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COVID- HGI worldwide meeting (R6)

Sep 20, 2021

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Study Design

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meta-analysis of 60 studies

from 25 countries

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Meta-analysis

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10 new loci

Identified

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23 loci in all

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Loci classification: severity vs susceptibility

We consider an assignment of variants into two groups based on whether they seem to affect susceptibility to SARS-CoV-2 infection or severity of the disease by SARS-CoV-2.

For this analysis, we meta-analyzed GWAS summary statistics from such versions of B2 (hospitalized covid vs. population) and C2 (infected vs. population) GWAS that only included those studies that had contributed some data to B2

Among the 10 new loci identified,

7 loci - SARS-CoV-2 disease severity

3 loci - SARS-CoV-2 infection

Matti Pirinen

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Heritability- low but significant across all three phenotypes (<1% on observed scale, all P-values < 0.0001)

COVID-19 phenotypes

h2_SNP

SE (h2_SNP)

Pval (h2_SNP)

LDSC intercept

SE(LDSC intercept)

Ratio

SE (ratio)

N_cases

N_controls

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Critical illness

0.0013

0.0004

0.0012

1.0192

0.0075

0.2695

0.1052

7641

1632197

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Hospitalized

0.0013

0.0003

1.468E-05

1.0213

0.0065

0.224

0.0681

18605

2490909

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Reported infection

0.0013

0.0002

8.032E-11

1.0302

0.0065

0.3125

0.0674

97783

2295876

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MR- 3 novel exposure - COVID-19 trait-pairs showed evidence of a causal association

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Multivariable MR

Preliminary results suggest that the risk effect of diabetes on COVID-19 is mediated by increased BMI