ABCD
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Genes & Health: Approved Research Studies
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StudyIDPrincipal Investigator(s)Project TitleLay Abstract
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S00015Nicholas Bass / Kamaldeep BhuiBrain consortium for Genes & Healtha. Please provide information on the aims of the proposed research including the research question(s) that you are aiming to answer and the health condition(s) under investigation

Over 1/3rd of the population experience mental health problems during their life. The most common of these are depression and anxiety disorders. Mental illnesses are usually caused by a mix of inherited as well as environmental factors. Neurological disorders, such as dementia, Parkinson’s disease and multiple sclerosis are similar, in that both genetic and environmental factors contribute to the development of the disease. The vast majority of genetic studies in psychiatry and neurology have focused on European ancestry populations. To help lead efforts to study these disorders in non-European ancestry, we would like to find out how many people in the Genes and Health study have mental health and/or neurological problems. Our aim is also to study the biological background of these disorders. To do this, we will use the medical records (primary care or secondary records linked to Genes & Health data for which ethical approval is already granted) to identify individuals who have experienced mental health or neurological problems of interest. We will then test whether any genetic variants are seen more often in these people. Some gene variants have already been linked to these problems through previous research and we will test whether they are also related to these illnesses in the participants of Genes and Health.

b. How will your research improve health?

Mental health and neurological problems are very common. We hope to identify specific needs with respect to prevention, diagnosis and treatment of individuals of Pakistani and Bangladeshi heritage. Our work could also identify genetic variants that cause these disorders. These could provide insights into the disease development and potentially suggest novel targets for drug development. The findings would have important implications for future research priorities, and for considering social, cultural and ethical issues in the recognition and care of brain disorders of varying types of genetic aetiology.

c. How does your research meet the other purposes of Genes & Health?

Taken together mental and neurological disorders (neuropsychiatric disorders) account for ~½ of the burden of disease. The lack of diversity in genetic studies of psychiatric and neurological disorders has been recognised as a severe problem. For example, there may be genetic variants in Bangladeshi and Pakistani populations that are very strongly associated with neuropsychiatric illness, which are completely absent in other populations. Failure to identify them would mean that there would not be an option to test for these variants in a clinical setting and valuable diagnostic information would be missed. Ultimately, the underrepresentation of non-European ancestry populations could affect who benefits from medical advances through genomic science. Variations by ancestry may hold clues to aetiology, and may also suggest finding of global health significance.

d. Please give a non-technical description of how the research will be undertaken

This study aims to understand the genetic causes of and genetic risks for neuropsychiatric illness in the Bangladeshi and Pakistani populations. This study may mean that we learn more about the genetic causes of these illnesses in all populations, as well as providing specialised knowledge of the illnesses in Pakistanis and Bangladeshis in particular. This information may help us develop new drugs or predictive tests. In the future it may be possible to identify the specific cause of neuropsychiatric illnesses in some families, which would mean that information can be provided about the risk for other family members, and maybe which drugs would be best to choose to treat the family members with mental illness. To do this work, we will go through the medical record data for Genes & Health participants and identify people with mental health and/or neurological problems. We will also look at other common diseases and demographic and social characteristics of the participants We will describe which groups are more often reporting mental health problems. We will then link this information with the genetic data from Genes & Health participants, which consists of data on millions of genetic variants. Our analysis will test whether specific genetic variations are seen more frequently in individuals with mental health problems. We will operate within the rules of Genes and Health. We will ensure that results of our genetic and laboratory studies are anonymous and that participants in the study cannot be identified through these results.

e. Please state the approximate number of volunteers to be included (i.e. whether the full cohort or a subset)

We request access to the full cohort.
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S00027Mike InouyeMeasuring the performance of transferability for published and machine learning-based polygenic scoresPlease provide information on the aims of the proposed research including the research question(s) that you are aiming to answer and the health condition(s) under investigation

Many diseases are preventable if they are detected early, which is easier if doctors know who is most at risk. For diseases like coronary artery disease, a common type of heart disease caused by narrow arteries, risk predictions are usually made based on risk factors like age, sex, family history, high cholesterol, weight and smoking habits. However, there is also a strong genetic component to the chance a person will develop coronary artery disease. The same is true for other diseases like diabetes, obesity and stroke.

Researchers have developed a new method to predict a person’s genetic risk for different diseases, called ‘Polygenic Scores’ (PGS). These PGS work by adding up the risk of a disease that come from small changes in lots of different genes. Predictions from these PGS can be combined with traditional risk factors like age and weight, to make a tool that predicts a person’s risk of developing a disease. Current PGS are often developed using genetic information from people of European heritage. Because there are genetic differences between people of different heritages, individuals whose ancestors come from Africa or Asia might not benefit from using existing PGS.

We aim to test how well PGS predict disease in South Asian people and develop new PGS that are better at predicting the risk of diseases in these communities.


How will your research improve health?

By using information from Genes & Health we will be able to identify and develop risk prediction tools that work for people of South Asian heritage. Tools that accurately predict the risk of diseases allows doctors to detect and treat diseases earlier.


Please give a non-technical description of how the research will be undertaken

We will use genetic and health information from Genes & Health to test how well a catalogue of published PGS predict the health of Genes & Health volunteers across a range of disease areas like coronary artery disease, diabetes and stroke. We will also use advanced machine learning techniques to develop PGS that work for people of different ancestries.

How does your research meet the other purposes of Genes & Health?

This will help us better understand the genetic basis for disease in South Asian individuals.
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S00035Marianne van den BreeInvestigating five large population-based cohort studies to understand the precursors of multimorbidity riskMultimorbidity is when an individual has two or more long term health conditions. Multimorbidity is common and carries a large social and economic cost, but despite this we understand little about the causes of multimorbidity, or how to treat it.

This project will combine information from five large research studies that follow participants over a period of time. The cohorts (Born in Bradford, Genes and Health, ALSPAC/Children of the 90s, UK Biobank, and the Danish study IPSYCH) have a total of around 680,000 individuals. Using information from all of these studies at once will help us study what social, genetic and environmental factors contribute to a person's risk of multimorbidity. Combining the information from these studies will allow us to see how the risk of physical and mental health problems influence each other. Importantly we will be able to see how these influences change over time or work differently in different age, ethnic or socioeconomic groups.

Our specific aims are to:

Understand how genetics contribute to physical and mental health multimorbidity
Understand how non-genetic factors such as living environment or lifestyle contribute to multimorbidity
Understand what factors might help protect against multimorbidity
Investigate how ethnic and economic health inequalities affect the development of health conditions
We hope that the results of this project will help develop better interventions for tackling multimorbidity that could be tailored to specific risk groups. This would benefit the whole of the UK, including the British South Asian population.
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S00037Catherine WilliamsonCombined genotype and phenotype screening for cholestasis of pregnancy and related hepatobiliary diseaseICP (a type of liver disease, also known as intrahepatic cholestasis of pregnancy) is the most common liver disorder of pregnancy, affecting the health of the unborn baby, and sometimes causing mothers to develop serious liver disease in later life. ICP is twice as common in South Asian populations compared to Caucasian populations, but little is known about why, as most research has been performed in Caucasian people.

Preliminary data have suggested that ICP in women of South Asian origin have a different genetic background compared with women of white European origin. My using the genetic and health record information in Genes & Health, this project aims to investigate the genetic cause of ICP in women in Genes & Health. At the same time it will try and find out whether the same genetic causes might also contribute to other types of liver disease in mothers and their families.

We will look for genetic causes of liver disease in pregnancy and will study whether the changes we find play a role in liver disease in the affected women or their relatives. The research will improve doctors’ understanding of what causes ICP in South Asians, and so hopes to improve long-term health of mothers, babies and other relatives.
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S00043Vincent PlagnolGenome-wide association analysis for coronary artery disease, atrial fibrillation, stroke and type 2 diabetes We are interested in the development of statistical models to predict the occurrence of diseases such as type 2 diabetes or heart attack, with the aim to integrate these models into healthcare in order to improve prevention and population health. A key component of disease risk is an individual’s genetic predisposition to this disease.

The impact of genetic variants on disease risk can be quantified using large cohorts such as Genes and Health, correlating the presence of these variants with disease outcome. This work is usually referred to as genome-wide association study, or GWAS. We therefore want to perform a set of GWAS for traits of interest, which includes heart disease, stroke and type 2 diabetes.

Genes and Health data are of particular interest because it is established that the correlations between variants and outcomes vary across ethnic groups. Genes and Health provides a picture of these correlations in the South-Asian population. These data will therefore benefit the development of genetically driven healthcare that benefits the South-Asian population, an ethnic group that has to date not received sufficient attention.
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S00046Nicole SoranzoPopulation-scale single cell RNA profiling in blood (CARDINAL)
The immune system is the body's first line of defence to infection. Some parts of the immune system act very fast, while other bits of the immune system react slower to but can build up a memory of previous infections. In some cases the immune system stop working, which is what causes diseases like arthritis or diabetes.

The activity of immune cells in the blood (and indeed, all cells in the body) is directed by messages encoded in the DNA in each cell. Small changes in the DNA between people can cause differences in how well the immune system works.

In this project we will obtain a small blood sample from volunteers and analyse whether and how small changes in the DNA in blood immune cells causes differences in how those immune cells work. By using lots of samples we will be able to understand how much variation there is between people.

This will help doctors and scientists understand diseases better, and help them to detect the early signs of disease earlier in South Asian and other populations.
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S00048Andrew MumfordGenetics of platelet count and size in people of Bangladeshi ancestryBlood platelets are a component of the normal blood clotting system, and are also involved in the development of cardiovascular diseases such as stroke and heart attack. The risk of developing cardiovascular disease partly relates to the number and size a persons platelets, which in turn are influenced by changes in a range of different genes. Understanding how changes in platelet genes lead to cardiovascular disease remains an important research goal.

It has been recognised for almost two decades that on average, the Bangladeshi and North Eastern Indian population have much larger and reduced circulating numbers of platelets compared to other populations. In order to help understand the reasons for this, we propose an exploratory study using genetic and laboratory information already collected from members of the Bangladeshi community for the Genes and Health project.

We will identify potential genetic causes using statistical techniques such as genome wide association study (GWAS) that has already been used to detect changes in platelet genes in other populations. The GWAS results will then be analysed in more detail by cross-referencing with other genetic databases and with existing scientific evidence about the function of genes in blood platelets. We expect this to give a shortlist of genetic changes likely linked to platelets specifically in people of Bangladeshi ancestry. This will enable future research to improve understanding about the genetic background of cardiovascular disease in the wider Bangladeshi population.
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S00050Amit KheraPolygenic risk - a focus on South AsiansSouth Asians are known to develop heart attacks at much higher rates than most other groups, but the causes of this difference are not well understood. Although South Asians make up 23% of the world’s population and number over 5 million in the United States, few studies have focused on this group. Is the higher risk of heart attack in South Asians due to risk factors we already know about – like diabetes – or are new risk factors more important for this group?

Understanding how things like lifestyle, genetics, upbringing, etc contribute to a person’s risk of having a heart attack is important because it helps doctors and patients make more informed choices. It’s important to include information about genetic and nongenetic factors. In the U.S., the most commonly used prediction tool for heart disease was developed without including any South Asians. Fewer than 1% of participants in genetic studies to date have been South Asian.

Our group has created new tools that predict risk of disease by looking at millions of places where one person’s genetic code differs from others, but these have also been based mostly on data from white individuals and perform less well in other groups.

In this project we will developing a way of predicting a person’s risk for heart attack specifically for South Asians. We will use genetic information available from large studies of South Asians to develop a polygenic score. We will then test how well it identifies people at high risk of heart disease. Successful completion of this research will improve our ability to predict risk of heart attack in South Asians.
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S00051Hilary MartinPopulation structure, demographic history and consanguinity patterns in Genes & Health, and their implications for disease riskPopulations from different geographical areas had different historical patterns of growth and migration, and different marriage patterns, including social practices like the biraderi system and consanguinity. Genetics can give us information about this which can be compared with historical records to understand the history, dynamics and structure of populations. Such population effects must be taken into account when searching for genes that influence disease risk, whether these be rare genetic variants that lead to severe birth defects, or common genetic variants carried by a large proportion of the population that can increase the risk of common diseases such as heart disease or diabetes. We will use the genetic data from G&H to investigate whether there are sub-populations that are genetically identifiable, how different they are from each other, when these separated, how their population sizes have changed over time, and how they relate to external reference populations from other datasets including biraderi groups identified from genetic and self-reported data in Born in Bradford. We will also investigate patterns of parental relatedness in G&H, using the genetic data to infer the relationship of each individual’s parents and comparing this to the self-reported relationship. We will look at how this differs between sub-populations and whether it changes over time. We will look for genes that have been subject to natural selection in particular sub-populations, and whether these are linked to particular traits in the health data. We will look at whether certain diseases and traits differ in prevalence between the sub-populations, and look for potential genetic causes of this. Finally, we will investigate whether marriages between unrelated individuals from the same sub-population (e.g. biraderi group) increase risk of rare genetic disorders in their children, and how this risk compares to the risk for children of first cousins. By shedding light on the genetic make-up of the British Pakistani and Bangladeshi populations, our study aims to contribute towards the drive for more personalised and population-specific medicine, that has the potential to reduce health inequalities. 
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S00055Eleftheria ZegginiGenetics of Osteoarthritis ConsortiumProject aims

The Genetics of Osteoarthritis (GO) consortium is a global collaboration with a focus on progressing our understanding of the genetic underpinning of osteoarthritis and related traits. We have recently completed the largest genome-wide meta-analysis (GWAS) for osteoarthritis and we investigated osteoarthritis at multiple joint sites. We identified 100 genomic regions that are associated with osteoarthritis. We have investigated which genes in these regions could be causal and have we identified a set of high-confidence effector genes.


We are now performing the second round of GWAS meta-analysis with an overarching aim to increase sample size and the ethnic diversity of the populations included.

How will the research be undertaken?

We will identify osteoarthritis cases and controls in the Bangladeshi and Pakistani individuals and perform a GWAS. The summary statistics will be combined with the summary results from all of the international cohorts contributing to the GO consortium and we will perform a number of meta-analyses; to investigate osteoarthritis across and within ethnic groups.


How will the results improve health for South Asian populations?

Osteoarthritis is a common debilitating disease with no curative therapy. To date osteoarthritis GWAS analysis has been mostly performed in cohorts of European descent, which means that our knowledge of osteoarthritis genetics in non-Europeans is restricted. Transferability of European genetic risk predictors into South Asians may not be appropriate. Here we aim to characterise the genetics of osteoarthritis internationally, this will not only improve the heath prospects for South Asians but also other ethnic groups. By combining results from multiple ethnicities, we are better armed to fine-map regions of interest and learn more about the biology of osteoarthritis.
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S00056George AllelicaDevelopment and Validation of Polygenic Risk Scores for common disease using individual level genetic data from diverse ancestry groupsPolygenic risk scores (PRS) are gaining attention as both a robust instrument for assessing an individual’s genetic liability for disease and as a critical tool for identifying individuals at high genetic risk of disease. Such tools pave the way for the use of genetic and clinical risk assessments to identify high risk individuals and on whom preventative interventions can be targeted. However, the vast majority of genomic and clinical datasets available for the development of such scores are of European ancestry. This is a problem for validating and deploying PRS in diverse communities because scores are population specific and in order to be transferred across populations need clinical datasets from broader population sets. This project aims to leverage new approaches for combining genome-wide association statistics, functional annotations and individual level genomic datasets from non-European ancestry groups to refine and improve PRS in South Asian populations. By using East London Gene’s unique
prospective cohort, we will refine PRS and disease risk models to increase their predictive performance in South Asian populations. The results will be published in peer-reviewed journals and will be used to develop population-scale risk assessment tools to be trialled in primary healthcare.
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S00057Gosia TrynkaEffects of Gene Knockouts in immune cellsThe immune system is formed by a complex network of cells and proteins that defend the body against infection and cancer. Dysregulation of immune cell function has broad implications and can lead to susceptibility to infections, severe immunodeficiencies or autoimmune diseases, such as rheumatoid arthritis or asthma.

We all carry millions of changes in our DNA, so called genetic variants, which determine a whole range of human traits, from our looks through to how our body responds to external pathogens. In this project we aim to understand how DNA changes in selected genes linked to the immune system affect immune cell function. To do so, we aim to recruit individuals who carry genetic variants in selected genes, collect blood samples and isolate immune cells to then characterise the effects of these variants on cell function. We will use the newest genomic technology that enables us to look at the activity of genes (including the genes with the genetic variants of interest) at a single cell resolution.

To date, the majority of studies have focused on the effects of genetic variation in European populations. However, findings from such studies may not apply well to other ancestries. Studying gene differences in the South Asian population allows us to uncover the gene differences specific to this population, and could inform new disease mechanisms and more effective drug therapies.
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S00059Ines BarrosoTowards a diabetes precision diagnosis approach with glycated haemoglobin (HbA1c) measurementGlycated Haemoglobin (HbA1c) is a measure of a person’s blood glucose (sugar) levels over an approximate 3 month period. HbA1c is measured in a standard blood test, and can be used for diabetes monitoring, and to diagnose people with, or at risk of, type 2 diabetes. The HbA1c test measures how much glucose is attached to haemoglobin, the oxygen carrying protein in red blood cells. The level of HbA1c is affected by a person’s average blood glucose, and how long their red blood cells live before they are replaced by the body. A red blood cell usually lives for 3 months, so the HbA1c test tells you someone’s average blood glucose during that 3 month period. However, there are many factors that affect the life of a person’s red blood cell, and therefore also the HbA1c level. These factors include anaemia but also genetic factors. Our team’s work has shown that there are specific genetic changes carried particularly by people of Asian and African-Caribbean origin that affect the accuracy of HbA1c. This finding is important as it might mean that using HbA1c may under-diagnose type 2 diabetes in people from these ancestry groups.

We would now like to study these genetic changes in more detail, and whether they affect people of Bangladeshi and Pakistani origin. This is important as type 2 diabetes is so common in people from these backgrounds, and an inaccurate HbA1c test result could have a significant impact. We will study both common and more rare gene changes that may influence HbA1c measurement. We will do this using genetic and health data from Genes & Health, looking at people with, or at risk of, type 2 diabetes, and those without the condition. We will combine our findings with those from other studies, and analyse data across them in a so-called ‘meta-analysis’. This will ensure our findings are robust and meaningful.

By doing this research, we will understand whether genetic information may help develop a more accurate HbA1c test result. This could be important in reducing the chance that someone is incorrectly diagnosed with type 2 diabetes or prediabetes when in fact they have normal glucose. It may also help us better predict who is most at risk of developing diabetes in the future.
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S00060Pradeep NatarjanGenome wide Discovery for Diabetes Dependent Triglycerides Associated Loci Replication in Genes & Health CohortElevated triglyceride levels often accompany type 2 diabetes, so we aimed to discover areas of the genome specifically linked to elevated triglyceride concentrations among individuals with type 2 diabetes vs. individuals without it. In a discovery cohort, we found found the opposite — a genetic region linked to lower to lower triglyceride levels in individuals with type 2 diabetes only. We want to test to see if these findings replicate in a separate group of South Asian individuals in the Genes & Health Study.
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S00061Timothy FraylingGenetics of Weight ChangeIn the UK, over half of all adults are currently overweight, with £10 billion spen each year on treating diseases that are common in people living with obesity, such as type 2 diabetes. While previous research has focussed on links between weight and disease, less is known about the importance of weight-change over time. For example, we do not understand the consequences of having a high BMI throughout life on disease risk compared with a normal BMI during childhood and a high BMI during adulthood (or vice-versa). Furthermore, one person’s weight may increase slowly while another person’s weight “yo-yos” up and down. The limited availability of weight data over time in large numbers of people means we know little about the link between weight fluctuation and disease that is independent from a single measure of a person’s weight.
We will combine people’s DNA data, health-care records, and lifestyle information to investigate weight-changes. We will test whether different patterns of weight- change make getting type 2 diabetes, for example, more likely, or whether simply being overweight is the main driver of increasing disease risk.
If patterns of weight-change are found to increase disease risk, then this work may help healthcare professionals and patients understand the importance of weight-change. It will also inform future studies that aim to prevent groups of people at risk of developing disease, such as type 2 diabetes.
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S00063Pradeep NatarjanGenome-wide Discovery for Preeclampsia and Gestational HypertensionThe hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) are linked to increased short-term risks to the mother and baby and to long-term risk of heart disease in the mother. The genetic underpinnings of these conditions remain poorly understood. We are hoping to incorporate the Genes & Health Study to improve our ability to discover new genetic regions associated with gestational hypertension and preeclampsia and thereby identify causal pathways that may imply new targets for prevention and treatment of these conditions.
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S00067Vincent Plagnol/Genomics PLCPolygenic Risk Score Performance ValidationGenetic data has the potential to transform health care, by identifying those at elevated risk of disease, enabling improved screening and prevention, and selecting effective treatment options. This is the case across a broad range of diseases, for example cardiovascular disease and type 2 diabetes, which have high prevalence in the South-Asian community (covered by Genes & Health).

However, much of the data underpinning this revolution in disease prediction has been generated in individuals of European descent. The results from such data cannot be readily applied to individuals of South-Asian ancestry, limiting broad adoption and widening an existing gap in access to modern genomic technology.

In this project we aim to assess how genetic predictors can be used in individuals of South-Asian ancestries living in the UK to identify those at elevated risk of a range of diseases. By engaging in this project we wish to improve and refine the design of these tools so that they become more usable and carry a higher degree of accuracy within South-Asian communities.
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S00071David RayGenetic links between (lack of) sleep and diseaseSleep and the circadian rhythm (or body clock) are essential to a healthy and happy life. We know that changes in our genes can results in changes in how we sleep, and also whether we prefer mornings or evening. These changes carry health consequences, we have found that the risk of particular diseases rises with preference for mornings (termed early chronotype).

Many studies have shown that things like shift-work which disturbs our body clock, also increase the risk of obesity, and type II diabetes. All this requires an understanding of what the body clock genes are doing, and we lack this information within the South Asian community.

For this purpose, we will collect the genetic data from Gene and Health resource and by using data analysis tools will identify the gene of interest, responsible for sleep, circardian rhythm and metabolism. The gene level analysis of target genes and their mutant variants that function at the interception of sleep/circardian rhythms and metabolism will determine the changes for human health. There is no research with South Asian origin people regarding sleep, or body clock function. We now want to see how the genes of the South Asian community may influence sleep and circadian behaviours, and risk of disease.
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S00073Adam Levine / Craig GlastonburyGenetics and cell shapes - Mechanism of disease in South Asian populationMicroscopic study of specific tissues shows variation of cellular composition between individuals. It is possible that some of this variation may also be due to genetic factors; however, this has never been studied before at scale. This study is designed to investigate the link of genetic data with the variation of tissue structures and cellular composition in order to understand mechanism of disease in people of genetic variation. Recent studies have shown that people from south Asian origin are more prone to different diseases because of their genetic makeup, that’s why to focus on the tissue linked genetic study will help to understand mechanism of disease in this population. For this purpose, the stained tissues slides of pathology importance named as whole image slide (WSI) and genomic data of individuals will be collected from Gene and health resource. The (WSI) will be interpreted by machine learning software specially design to observe tissue variations. This data will be compared with genetic data of the individuals and will further analysed by different computational data analysis tools, which will result in bringing the co-relation between genetic variation and change in tissue structure/cellular composition. As a result of this study, we hope to develop deeper understanding of mechanism of disease in people from South Asian origin.
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S00076Shai CarmiEstimating sex-specific mutation rates based on runs of homozygosityOur bodies are made up of trillions of cells, each of which contains DNA - long strands of genetic material containing instructions that tell the cell what to do. We inherit half of our DNA from our mother (via the egg) and the other half from our father (via the sperm). When DNA is passed down from our parents, some changes occur in it – on average, each of us inherits about 70 changes that were not seen in the DNA of either parent. Estimating the rate of these DNA changes is key to understanding how genetic variation is generated within and between populations. It is known that the rate of these DNA changes varies between the sexes, but it has been difficult to directly estimate the rate in men and women separately. We developed a statistical method to estimate the sex-specific rate of DNA changes based on segments of DNA that an individual inherits from a recent common ancestor through both parents. This typically happens when the parents are related as second cousins or closer, which is common in Genes & Health. Our method does not require the DNA sequence of any additional family member. We aim to use G&H data to test our method on real data.
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S00077Brent RichardsUsing human genetics to identify and validate drug targets through changes in phenotypic variance across ancestries.The genes that we inherit from our parents can influence our risk of disease. This genetic information, encoded in DNA, can also help to understand causes of disease. When these causes are identified, they can also act as targets for interventions that lessen the risk of the disease or improve its outcome. These interventions can be a change in our behaviours, such as how much we exercise, or what we eat. They can also be interventions such as medicines. Here we propose a program of research to attempt to use genetic information to identify and validate appropriate interventions to decrease risk of disease and reduce its consequences.

Considerable work has been done to identify the genetic causes of disease in people of European ancestry. This is largely because data are available for people of this ancestry in large scale. However, less work has been undertaken to identify the unique causes of disease in other ancestries, such as people of South Asian ancestry.

Our aims are therefore to identify the genetic causes of disease in the South Asian ancestral group, since the rates of different diseases vary across ancestral populations and their causes may be different. Once we begin to understand the causes of disease in the South Asian population, we may begin to better identify points of intervention to lessen the consequences of such diseases.
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S00088Andrea GannaGenCOST ConsortiumHealthcare costs continue to rise worldwide, and in 2018, global healthcare spending reached $8.3 trillion, or 10% of the global gross domestic product. Accurate measurement of healthcare costs associated with different risk factors and health outcomes is important to prioritize public health promotion and prevention programs. Moreover, healthcare utilization, and associated healthcare costs, can be used to compare the impact of risk factors on individual health burden in a disease-agnostic manner. Thus, analysis of healthcare costs is of significant interest from an epidemiological, public health, and policy perspective.

In this project we aim to study the impact of genetic factors on healthcare cost. There are three major motivations. First, healthcare costs can provide an objective measure of morbidity. Thus, genetic associations with healthcare costs can help identify biological pathways that are implicated in overall health maintenance. Second, implementation of genetic-based screening tools in a clinical setting requires cost-effectiveness evaluations. Estimating the relationship between genetic risk factors and healthcare costs can help estimating the cost-effectiveness of novel genetic-based interventions. Third, genetic associations with healthcare costs can be used to inform the causal relationship between modifiable risk factors and healthcare costs using statistical genetic approach.

The Genes and Health cohort is one of the most important sources of data in South Asian populations, as most the participants in the consortium are of European ancestry. Inclusion of the Genes and Health will improve the generalizability of our research findings, which could be directly informed in the clinical practice of South Asian populations.
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S00089Elias AllaraThe genetic determinants and biomedical consequences of iron-related traits in a large population of South AsiansIron is an essential element for human health and is a component of hundreds of proteins and enzymes that support essential biological functions. Iron deficiency is the most common type of iron imbalance, affecting more than 2 billion people worldwide and leading to anaemia in approximately 500 million people. Recent research has also identified potential links between iron deficiency and cardiometabolic/infectious diseases.

Genetics can shed light on the potential causes of iron disorders and can also improve our understanding of their clinical consequences. Iron research to date has, however, focused mostly on participants of European ancestry and on common genetic polymorphisms.

Using data from the Genes & Health study, we aim to explore the genetic determinants of iron traits and their impact on health in South-Asian populations. To achieve this, we plan to combine the results from Genes & Health with those from other studies that include South-Asian participants, such as UK Biobank and BELIEVE. Through this research, we hope to gain a better understanding of the genetic architecture of iron homeostasis, the causes of iron disorders such as iron deficiency, and the effects of iron on clinical health outcomes. The results of the study could lead to improved insight into processes that regulate iron and, potentially, improved health outcomes for South-Asian populations.
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S00091Sarah Finer and Steve O'RahillyIdentification and characterisation of rare, functional variants of potential relevance to endocrinology, neuroendocrinology and metabolismWe are a team of doctors and scientists that study people carrying rare mutations in genes that we think may be relevant to human metabolic health. Specifically, we look for rare spelling mistakes (mutations) in the DNA and determine if these spelling mistakes alter the function of the proteins they serve as templates for. We compile prior knowledge and information from laboratory studies to decide which of these spelling mistakes may be important in controlling the body’s metabolic health. When we think the spelling mistakes are likely to be important, we wish to study these further in Genes & Health volunteers who do and do not carry them, We do this by studying the electronic health records of volunteers, and also by inviting some volunteers to have a clinical assessment. This clinical assessment typically includes taking a medical history, performing a brief clinical examination (for example measuring height, weight, and waist circumference) and doing some blood tests. In some cases, depending on the gene we are studying, we may invite people to more detailed studies, e.g. a glucose tolerance test which studies how the body responds to drinking glucose, or a DEXA scan to assess body fat.
This application seeks to advance our previous work by expanding our studies of genes related to metabolism and the endocrine system (hormones and their pathways) using detailed genetic investigations (exome sequencing) performed by Genes & Health. We will prioritise our work on several genes of interest where we think a spelling mistake could help us make an important new discovery. Our team has proven track record of using this approach to discover new genetic causes of human disease and to develop healthcare services and treatments that can benefit those affected. As such, we expect this work will benefit the communities involved in Genes and Health study directly, and that these findings will be of direct relevance to other South Asian populations that are likely to carry similar gene mutations.
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S00095Eleftheria ZegginiType 2 Diabetes Global Genomics Initiative (T2DGGI)Type 2 diabetes is a complex disease and the risk of developing it is affected by our lifestyle and diet. We also know that type 2 diabetes is also associated with our family history and our genetic makeup and furthermore individuals of south Asian ancestry have a higher risk of developing type 2 diabetes irrespective of their lifestyle and diet. We have carried out a large genetic study in many people from different ancestry groups to find out which of our genes are important for causing type 2 diabetes. We have found many genetic changes associated with a risk of having type 2 diabetes. To try and find out how these genetic changes affect type 2 diabetes we have grouped them depending upon how they might cause type 2 diabetes. For example, one genetic risk group is found in individuals who are overweight and we know that increased weight is a risk factor for type 2 diabetes. In total we found 8 different genetic risk groups. We would like to test if these groups are associated with additional problems that can happen in people with type 2 diabetes. For example, coronary artery disease, stroke and eye problems are commonly found in people with type 2 diabetes. The genetic risk groups were constructed using information from different ancestries although there were not many individuals from south Asian. As the prevalence of type 2 diabetes is higher in south Asians we would like to find out if these risk groups are important in south Asian individuals. Therefore, we would like to measure these genetic risk groups in Genes and Health data to see if we can predict who is more likely to suffer from additional problems if they have type 2 diabetes.
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S00096Michela Carlotta MassiThe genetic architecture of longitudinal biomarker trajectories and their relationship with complex diseasesThe project will focus on developing and applying novel methodologies to study the genetic architecture of biomarkers’ evolution over time, and their relationship with clinical outcomes of interest. To do that, primary care and hospital administrative data will be exploited to derive longitudinal biomarker trajectories. Modelling Gene-biomarkers associations (considering single or multiple trajectories at a time) will result in the identification of representative biomarkers trajectory groups, and their association with individuals’ genetic background. The considered biomarkers will include BMI, cholesterol, blood pressure, and others. Further clinical time varying information will be retrieved and included in modelling gene-biomarker relationships, to adjust for exogenous confounders influencing biomarkers’ evolution, such as prescriptions and health conditions. Then, further analyses will identify the effect of specific trajectory groups on the clinical endpoints, that will include ischemic stroke, coronary artery disease and diabetes (derived from primary care and hospital data).

This project will provide novel insights on how biomarkers evolution over life time can increase the risk of adverse events and/or diagnoses. Applying the proposed pipeline on UK Biobank data and Gene & Health will enrich the ethnic diversity of the studied population, leading to more robust discoveries. Moreover, stratifying by ethnicity can lead to South Asian-specific discoveries, and serve as a tool for early disease detection and intervention.
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S00097Arslan A. ZaidiGenetic and phenotypic correlates of mitochondrial DNA copy number in South AsiansMitochondria are important components of the cell and mitochondrial dysfunction can lead to mitochondrial diseases. Mitochondrial dysfunction also seems to underlie common diseases such as cardiovascular diseases. But the mechanism underlying such associations are not well understood. We want to understand the role of inter-individual variation in the number of copies of mitochondrial DNA in a cell (mtCN) – one potential biomarker of mitochondrial activity and function – in contributing to variation in health-related traits among South Asians. We are particularly interested in studying this for cardiovascular diseases, which have a higher prevalence and earlier onset among South Asians. To accomplish this, we will (i) analyze the genetics of mtCN, (ii) study with which traits mtCN is associated and evaluate whether mtCN-phenotype associations are causal. Because of endogamy and consanguinity, the genetic variation among South Asians is quite complex and can lead to spurious results in population-based genetic studies. This can limit our ability to properly identify disease causing mutations and ultimately our ability to diagnose individuals with a higher-than-average genetic risk of disease among South Asians, further exacerbating existing inequalities in medical genetics. While there are many methods available to address this problem, we have shown that such methods are not always effective, particularly in populations with a complex genetic structure. Thus, we also seek to (iii) improve tools to discover disease-causing mutations and predict the genetic risk of disease in South Asians for early screening and diagnosis.
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S00099Jennifer JardineUnderstanding links between pregnancy complications and long-term health: a multi-ethnic approachWomen in the UK, particularly women of South Asian background, experience higher levels of illness such as heart disease. While tackling these inequalities is a government priority, not enough is known about how to do so.

Illnesses in pregnancy, such as high blood pressure and gestational diabetes, are associated with increased risk of long-term illness in women after birth. However, at present, it is unclear which women at increased risk, and what we can do to change that risk. Current screening tools do not always incorporate what we know about pregnancy complications to predict a woman’s long-term health.

This study seeks to improve our understanding of the link between pregnancy-related illnesses and long-term health in South Asian women, by using Genes and Health data. The study will use women’s health records and genetic information to understand what happens to women with a pregnancy-related illness after pregnancy – including which women develop a long-term illness, and how soon.

The results of this study will both improve existing understanding of health for women after pregnancy and in the long term. The study will then lead on to further research to develop new tools to identify women at increased risk and suggest actions to change that risk. These can be used in clinical practice to improve women’s health.
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S00103Michael BarnesClinically Informed Drug Target PredictionDrug target identification is a crucial step in discovering new drugs. Today, genomic data is playing an increasingly important role in this process. Our project aims to create a machine learning model that uses clinical information to predict and prioritize genomic targets that are likely to be safe and effective for drug development. By training the model with data from approved drugs and clinical trial safety records, we teach it to recognize patterns connecting genetic traits and variations to the success of clinical trials. This allows us to predict and prioritize potential drug targets based on their suitability for drug development. The Genes and Health (GH) data is vital for our model as it provides valuable information about genes that helps us identify safer and more effective drug targets. There are two main reasons for this. Firstly, the GH data includes a higher rate of rare gene knockouts in south Asian populations, which helps us understand gene function better. Secondly, by fine-tuning the model to specific populations, we can explore how drug responses differ among different groups of people. This enables us to develop drugs that cater to populations that have been historically underrepresented in medical research and databases. The GH data is a valuable resource that helps us work towards this goal, particularly for South Asian populations.
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S00104Martin TobinGenomics of long-term conditions in South AsiansLong-term conditions – individually and together – impose a significant health burden in South Asian populations. In some cases, a person may have two or more conditions. This can occur, for example, where the same genes and proteins are involved in causing more than one condition, or when a treatment for one condition causes or unmasks a different condition. Studying the genetic causes of long-term conditions helps to understand why these conditions occur, what makes these conditions progress, and why some people respond better to drug treatments than others. Whilst such studies in mostly European ancestry populations are already improving understanding and driving the development of new medicines, South Asian populations remain under-represented in genetic studies. To generate research evidence relevant to improving, preventing and treating long-term conditions in South Asian populations, we will study the genetics of these conditions in Genes & Health, using data from DNA, linked GP and hospital electronic healthcare records, and questionnaires.
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S00109Killian DonovanGenetic determinants of chronic kidney disease progressionChronic kidney disease affects about 3 million people in the UK. It causes kidney function to decline slowly overtime, and eventually people with chronic kidney disease may need dialysis or a kidney transplant. It disproportionately affects people of South Asian heritage, who account for approximately 14% of patients on dialysis in the UK [1]. There are some treatments that slow the rate of progression of chronic kidney disease, but the rate of progression still varies a lot between patients and the reasons for this are not well understood. We think that genetic differences between people may play a role.

The purpose of our research is to use patient samples and data which has already been collected in the Genes and Health study and other studies like it to identify genetic factors that are associated with declining kidney function among people with chronic kidney disease, and to see if these factors are different in different ancestry groups. This will help us understand kidney disease better, and hopefully help to develop new treatments. Crucially, it may help us identify whether there are genetic reasons for the differences in kidney disease between people of different ancestry background.
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S00111Eleftheria ZegginiGenetics of OsteoarthritisProject aims
The Genetics of Osteoarthritis (GO) consortium is a global collaboration with a focus on progressing our understanding of the genetic underpinning of osteoarthritis and related traits. We have recently completed the largest genome-wide meta-analysis (GWAS) for osteoarthritis across multiple joint sites. We identified more than 900 genomic regions that are associated with osteoarthritis. We have investigated which genes in these regions could be causal for osteoarthritis and we term these high-confidence effector genes.

How will the research be undertaken?
We have identified a number of the high confidence genes that are new GWAS discoveries that we think are important in osteoarthritis but we don’t know much about the biology of the gene and how they could cause osteoarthritis. To try and help us to understand this we have selected the high confidence effector genes that also contain a particular type of genetic variant; one which can cause the gene to not function correctly. We will identify Genes and Health individuals that harbour this type of genetic variant in these genes and we will look to see if these individuals also have any conditions related to pain or the musculoskeletal system. By linking the gene to any new pain and/or musculoskeletal findings we may get hints at new biological ways in which osteoarthritis develops.

How will the results improve health for South Asian populations?
Osteoarthritis is a prevalent and disabling condition lacking a definitive cure. Our aim is to comprehensively examine the genetics of osteoarthritis and enhance health outcomes on a global scale.
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S00119Chris Wai Hang LoDissecting the genetic contribution to depression and antidepressant responseDepression is a pervasive mental health disorder that is characterized by persistent feelings of sadness, hopelessness, and disinterest in previously enjoyed activities. One in six people likely to be diagnosed at some point in their life, and the burden is high in South Asian population. Rates of depression are rising, and depression presents a significant public health concern. Antidepressant medications are the cornerstone in depression treatment, aiming to alleviate symptoms and improve overall functioning. Despite their widespread use, we know little about how antidepressants work, and who they work for best. There is much scope for improvements in prescribing, as only about one-third of patients respond to the first antidepressant they are prescribed.

In Genes&Health, we will identify the genetic predictors of response to antidepressants, by combining electronic health records with prescribing data and genome-wide genotype data. Previous analysis of clinical studies has identified a genetic underpinning to response to antidepressants, but small sample sizes prevented the identification of specific genetic variants that influence response. Using the large resource of prescribing records in Genes&Health, we will identify those who respond or who do not respond to antidepressants and assess their genetic differences. We aim to identify the genetic predictors of response to antidepressants, building evidence for personalised prescribing, where a choice of antidepressant is based on personal factors including genetics, enabling people to receive more effective treatment for depression.
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S00120Julia ZollnerThe genetic architecture of preterm birth in a British-South Asian CohortThis research project seeks to explore why some babies are born too early, known as preterm birth, within a British South Asian community. Preterm birth can lead to health problems for babies both immediately after birth and later in life. Understanding why it happens is crucial to preventing it. Increasingly there is evidence of genetic associations with preterm birth. The British South Asian community has higher preterm birth rates compared to other groups, but genetic risks in this cohort has not been studied previously.

My study will use data from the Genes and Health cohort, which includes genetic information from thousands of British South Asian individuals. By examining this data, I aim to uncover genetic factors that might contribute to the risk of birthing a baby preterm. Specifically, I will study common and rare genetic variations that could influence conditions like preterm birth without prior warning and preterm birth due to early breaking of waters. I will focus on cases occurring before 36 weeks of pregnancy which carry the highest risk to the baby. My goal is to better understand the biological reasons behind preterm birth in this particular group. This knowledge could lead to the development of new ways to predict and potentially prevent preterm birth, not only benefiting the British South Asian community but also improving our overall understanding of preterm birth across all populations.
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S00121Sadaf FarooqiGenetic basis of body weight regulation: severe obesity, persistent thinness and related traitsObesity is defined as an excess of body fat that adversely affects health due to the increased risk of type 2 diabetes, cardiovascular disease and certain cancers. Recent changes in our environment such as the wide availability of high calorie, highly palatable foods and more sedentary lifestyles have driven the rise in obesity prevalence. However, there is strong evidence that within a population that shares the same environment, the variation in BMI is in part genetically determined.

Recent decades have seen advances in understanding the fundamental biology of body weight control, with the identification of the hormone leptin which is made by fat cells. Candidate gene studies showed that mutations disrupting leptin, its receptor and downstream targets in the brain cause severe obesity that begins in childhood. Many of these genes work on the control of appetite. We have shown that discovery of the genetic variant can lead to effective treatment for patients in some cases.

Our aim in this project is to see if the genes we have found to contribute to body weight regulation in people with obesity, and also with thinness, can affect weight and BMI in the Genes & Health cohort. We will learn more about the role of these genes in the control of weight, and other closely related measurements such as blood pressure, cholesterol levels and the risk of diabetes. We may be able to use this information to design new treatments to help people who struggle with their weight, and contribute to research into closely related health issues.
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S00122Iftikhar J. Kullo Improving polygenic prediction of coronary heart disease in South AsiansHeart and blood vessel diseases and related risk traits (such as obesity, diabetes, and hypertension) are one of the leading causes of death worldwide. Risk scores that are made up of genetic markers in the human genome, i.e. polygenic risk scores (PRS), are measures that reflect one’s genetic risk for a particular health condition. However, application of these scores to different racial/ethnic groups, such as South Asians, have been challenging since PRS were mainly developed using white participants. We aim to create PRSs that work better for diverse populations, including South Asians. We will use genetic and health data from South Asian individuals participating in Genes & Health study. We will look at several heart-related conditions like obesity, diabetes, hypertension, and heart disease. Using a variety of methods, we will develop new PRSs tailored for South Asians and also explore ways to combine PRSs with other risk factors, like rare genetic variants and clinical risk factors, to improve risk prediction further. By advancing PRS methods and focusing on an understudied high-risk group, our research could lead to better heart disease prediction and prevention for people of all genetic ancestries, including South Asian individuals. More accurate risk scores could help physicians identify high-risk patients earlier and recommend personalized interventions.
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S00126.Paul McKeigueEffects of rare variants in core genes for disease identified by genome-wide aggregated trans effects analysisWe have developed a new method of genetic analysis to identify core genes on which the effects of other genes coalesce to cause disease. We have used this method of genetic analysis to identify core genes for diseases including type 1 diabetes, in which the immune system attacks the cells that make insulin to control blood sugar, type 2 diabetes, in which fat deposited in various organs disrupts the control of blood sugar, and coronary heart disease.
The overall aim of this project is to lay the basis for developing new drugs that target the proteins encoded by these core genes to treat these diseases. The specific objective is to establish whether rare variants that alter the function of these core genes are associated with disease. This is especially relevant to the health of South Asian populations, in whom rates of type 2 diabetes and coronary heart disease are higher than in people of European ancestry.
For each core gene we shall test whether people with 1 or 2 copies of rare variants that switch off the gene have higher or lower risk of any disease than people without these variants. Where our research indicates that blocking the protein encoded by the gene might help to treat the disease, we shall test whether possession of 2 copies of rare variants in the gene that switch off the protein is compatible with healthy life.
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S00127Nicole SoranzoCARDINAL ScaleBioSuper deep single cell analysis of frozen PBMC from the CARDINAL project. See S00046.
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S00138William NewmanExtending pharmacogenetic testing to reduce aminoglycoside induced hearing lossPeople respond differently to their medicines. In some people there is a higher risk of side effects or the medicine not working as well as hoped. We know that genetic changes can be important in how people respond to medicines. This is called pharmacogenetics. For example, about 1 in every 500 people will experience severe hearing loss if they take a common antibiotic called gentamicin due to a genetic change. This drug is used to treat or prevent infection in newborn babies. With a small company called Genedrive, we have developed a bedside genetic test that can provide a result in 25 minutes from a cheek swab and ensure that babies get safe antibiotics. This test is now being rolled out in neonatal units across the UK and looks at the most common change in this gene (we call it m.1555A>G). The majority of the babies in whom we have prevented hearing loss to date have been of Pakistani ancestry suggesting that the genetic change is more common in this population. We also know that there are two other genetic changes (called m.1095T>C and m.1494C>T) that increase the risk of hearing loss, but these are not currently tested for. We want to develop an updated test that can detect these other gene changes and prevent hearing loss in more babies. We know that some participants in the Genes and Health study carry these rare genetic changes. If they provide a blood and cheek swab samples this will help us to develop a new test that can be used in neonatal units and check the accuracy of these tests.
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S00139Huw MorrisAnalysis of Sequence Variation in Known and New Neurological Disease GenesThere are two parts to this study: firstly, understanding what happens when people in the general population
inherit variants in genes that are known to cause neurological disease such as Alzheimer’s and Parkinson’s; and
secondly, identifying new genes that can cause neurological disease, particularly in non-European ancestry .
1) Variation in neurological disease genes:
Some neurological diseases, such as Parkinson’s disease and Alzheimer’s disease, can be caused by an
increase in harmful gene activity. To prevent this, many clinical trials seek to reduce harmful gene
expression; however, it is hard to predict the safety of this approach before implementing it. One way
of doing so is to observe the health outcomes of individuals who have naturally reduced gene function.
Such participants may be found in studies such as ELGH and can be crucial in helping us improve the
treatments for those with neurological diseases. Understanding the biology of Parkinson’s and
Alzheimer’s will help to develop new treatments which will be relevant to the South Asian population
and help us to understand possible side effects.
2) New gene identification:
We have recruited young-onset patients with neurological diseases from East London to two studies:
the 100k Genomes Project and the Parkinson’s Families Project in collaboration with Dr Louise Hartley,
Paediatric Neurologist at the Royal London Hospital. Understanding the prevalence of rare harmful
genes within the Pakistani and Bangladeshi population in East London is essential for accurately
assessing their role in causing neurological diseases. Our ongoing commitment to the identification of
novel genes associated with neurological disease will b
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S00141Krina ZondervanGenetic Determinants of Endometriosis, Adenomyosis, Uterine Fibroids, and Related Symptoms in Diverse PopulationsThis research project aims to better understand the causes of three common but often misunderstood health conditions that affect the womb: endometriosis, adenomyosis, and uterine fibroids. These conditions can cause a range of difficult symptoms, including heavy periods, pelvic pain, tiredness, and sometimes problems with fertility. They are often underdiagnosed or diagnosed late, especially in South Asian women, which can lead to years of suffering without proper care. Our project will study the genetic makeup of people who have these conditions to find out if certain inherited factors make some individuals more likely to develop them. We also want to understand why symptoms vary so much between people and whether genetics can help explain these differences. To do this, we will use health data and genetic information from Genes & Health and other large health studies, and we will combine this with new methods that group people based on their symptoms. This will allow us to look more closely at different patterns of disease and find genetic signals linked to specific symptoms like pain or heavy bleeding. Understanding the genetic causes of these conditions in British Bangladeshi and British Pakistani communities is especially important because research in these groups has been very limited. By including people from diverse backgrounds, our findings will be more accurate and relevant to everyone. In the long term, this research could help develop better tests for early diagnosis, more personalised treatments, and fairer healthcare for South Asian women affected by these common but neglected conditions.
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S00145Abigail LayUsing human genetics to identify causal molecular drivers of type 2 diabetic kidney diseaseDiabetic kidney Disease (DKD) is a major, global health problem and leading cause of kidney failure worldwide. Up to 40% of people with diabetes will develop kidney disease (i.e., ‘DKD’) during their lifetime, and almost one in three people who need dialysis, or a kidney transplant, have diabetes. New, better, treatment strategies are urgently needed to prevent or reverse DKD, and ultimately, reduce the number of people progressing to kidney failure. We first need to better understand what causes DKD. Our aim is to understand the impact of our genetic makeup on DKD, by perform a large ‘genome wide’ study. Our study will identify genetic variants specific to South Asian populations, as well as across multiple population groups, that increase the risk of developing DKD. These results can be used clinically in future, to identify individuals with diabetes that are most ‘at risk’ of developing DKD, for early, targeted, treatments to ultimately prevent or reduce the progression to kidney failure.
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S00146Gerome BreenPsychiatric, psychology, and treatment response genetics in Genes & Health.Mental health conditions such as anxiety, depression, and eating disorders are increasingly common. These conditions significantly affect people's quality of life, daily functioning, and impact their families and communities. Moreover, these disorders are associated with a heightened risk of physical health problems.

In the UK, people of South Asian heritage experience higher rates of mental health difficulties compared to White individuals but are less likely to seek professional help. When South Asian individuals do access treatment, outcomes remain poorer; recovery rates following NHS Talking Therapies are 44% for Asian patients compared to 50% for White patients3 (specific ethnicity categories were not detailed). Additionally, emerging evidence suggests that eating disorders, particularly binge eating disorder, are prevalent yet significantly underdiagnosed and undertreated in South Asian communities.

It is crucial that South Asian populations are adequately represented in mental health research, especially in studies of eating disorders, to ensure equitable benefits from clinical advancements. Our research aims to identify genetic and environmental factors associated with anxiety, depression, eating disorders, and treatment responses in South Asian individuals. We will also investigate side effects associated with antidepressant drugs and other psychiatric medications, to understand their impact on treatment adherence and overall health outcomes. By combining NHS psychological therapy records, hospital data, genetic data, and detailed questionnaire responses from participants in the G&H study, we aim to enhance the understanding of mental and physical health interrelationships. This comprehensive approach will contribute to improved, personalised, and culturally informed mental healthcare for South Asian communities and beyond.
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S00150Rohan SundramoorthiGenetic Architecture of Inflammatory Bowel Disease in South Asian PopulationsThere have been major advances in our understanding of the genetics of inflammatory bowel disease (IBD) over the past decade. However, genetic studies so far have focused on individuals of white ethnicity. Ethnic minority communities make up over 11 million people in the UK, and IBD is becoming increasingly common in these groups. Yet, they remain underrepresented in research. This lack of inclusion limits our understanding of IBD and makes it harder to provide effective care for everyone. In our recent study, using data from the NIHR IBD Bioresource, we analysed clinical information from over 30,000 IBD patients across the UK. We found that South Asian patients develop IBD at a younger age and experience different patterns of disease. To better understand these differences, we now plan to combine genetic and clinical data from the IBD Bioresource with information from the Genes & Health project. This will be the largest genetic study of South Asian IBD patients in the UK. Our aim is to identify genes linked to more severe disease and those that may affect how people respond to treatment. These insights could lead to a better understanding of how IBD develops and enable more personalised treatment through genetic testing in the South Asian population. By focusing on under-represented ethnic minorities, we hope our research will support a more personalised and inclusive approach to IBD care, and highlight the urgent need to address these gaps within IBD research.
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S00155Alasdair WarwickGenetic associations for sight-threatening diabetic retinopathy in British South Asian populationsDiabetic eye disease (diabetic retinopathy) is a major cause of blindness that affects people with diabetes when high blood sugar levels damage the small blood vessels in the back of the eye. While we know that factors like blood sugar control and how long someone has had diabetes affect the risk, it is unclear why some people develop sight-threatening complications while others do not.

People of South Asian background (including British Bangladeshi and British Pakistani communities) are at particularly high risk of developing diabetes and its complications, but there has been very little research into the genetic factors that might influence their risk of diabetic eye disease.

Our study aims to identify genetic variations that increase or decrease the risk of sight-threatening diabetic retinopathy in South Asian populations. We will do this by linking genetic information from the Genes & Health study with detailed eye screening records from the North East London Diabetic Eye Screening Programme, creating one of the largest genetic studies of diabetic eye disease in South Asian populations to date.

By understanding which genetic factors influence disease risk, we hope to:
- Identify people at highest risk who might benefit from more frequent screening or earlier treatment
- Discover new biological pathways that could lead to better treatments
- Help doctors provide more personalised care based on individual genetic risk

This research will directly benefit British Bangladeshi, British Pakistani, and other South Asian communities by improving our understanding of why diabetic eye disease affects these populations disproportionately. Importantly, many genetic discoveries are expected to be relevant across diverse ancestries, meaning our findings could also inform better prevention and treatment strategies for people of all ethnic backgrounds.
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S00159Michael SkinniderDiscovery of unknown metabolites linked to human disease and the plasma proteomeAlthough it is now possible to comprehensively measure the DNA, RNA, and protein molecules in a given sample, it remains very challenging to identify all the small molecules in the same sample. Small molecules include building blocks of cells such as amino acids and lipids, plant or animal-derived molecules that we consume through our diet, and molecules that drive human diseases such as cancer. We have recently developed a computational approach to discover the unknown small molecules that can be detected, but not identified, within human samples. We will apply this approach to discover unknown metabolites in the Genes & Health cohort. Working with Genes & Health study team members, we will then link the abundance of these unknowns to genetic factors associated with health and serum proteins. Our work will provide a new data resource to better understand the metabolic and genetic factors that are linked to health and disease in the study population.
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