Welcome!
Community-curated standards & an infrastructure for predicted effector gene lists
Why does this matter?
Two approaches…
…One objective
International team…
contributing to this effort
Our Objectives
Our Outputs
Strawman
PEGASUS
What does this mean?
Date (2024-25) | Publication & phenotype(s) | Size / ancestry of meta-analysis | Evidence sources combined in the gene-ranking step | Metric / rule published (files in supp. data unless noted) |
10 Feb 2025 | Schipper M et al. “Prioritizing effector genes at trait-associated loci using multimodal evidence” — Multi-trait (UK Biobank + GWAS Catalog) | 14,000 GWAS loci, pan-trait | Fine-mapping (SuSiE), coding variant annotation, convergence layer (co-expression, Reactome/GO pathways, PPI) | FLAMES score (0-1 probability per gene/locus; TSV on Zenodo) PubMed |
3 Jan 2025 | Dang X et al. “Gene-level analysis reveals the genetic aetiology and therapeutic targets of schizophrenia” (Nat Hum Behav) | 144 K cases / 1.3 M ctrls, multi-ancestry | MAGMA gene-level p, PoPS, TWAS (brain GTEx & PsychENCODE), chromatin-interaction links | Integrated gene score (normalized −log10 p across all sources) — ranked list of 298 genes (Supplementary Table 3) PubMed |
21 Nov 2024 | Zheng S L et al. “Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy” (Nat Genet) | 14 256 cases / 1.1 M ctrls (European + multi-ancestry) | PoPS, distance-to-lead SNP, OpenTargets V2G, multi-tissue TWAS, rare-variant colocalisation | Omnibus prioritisation score (weighted sum; sheet in Supplementary Data 8) Nature |
04 Mar 2025 | Henry A et al. “GWAS meta-analysis of heart-failure and its subtypes” (Nat Genet) | 90 K cases / 1.3 M ctrls, multi-ancestry | PoPS, OpenTargets V2G fine-map score, multi-tissue S-MulTiXcan TWAS | Two-step rank: top gene per locus if best in ≥1 metric; 356 ranked genes (Extended Data Table 5) Nature |
16 Apr 2025 | Lange L M et al. “Prioritizing Parkinson’s disease risk genes in GWAS loci” (npj Parkinson’s Dis.) | 49 K cases / 2.4 M ctrls; Eur. + E.Asian | PoPS, nearest-gene distance, exonic credible-set variants | PD-PoPS rank: PoPS-top gene intersected with distance / coding evidence; 46 high-confidence genes (Table 2) Nature |
24 Apr 2025 | Li H et al. “Multi-ancestry seqGWAS of C-reactive protein (CRP)” (Nat Commun) | 513 273 WGS samples (TOPMed + UKB + AoU) | Cross-ancestry FINEMAP, PoPS, gene-based SKAT-O tests | PoPS-enriched list: 151 genes ranked by PoPS then SKAT-O significance (Supp. Data 9) Nature |
Our community is still churning out large-scale GWASs with gene prioritization
▲ Rank | Publication (Year) | Gene-prioritisation metric released | What makes the metric “curated” | Scope / data breadth |
1 | Schipper et al. “Prioritizing effector genes at trait-associated loci using multimodal evidence” Nat Genet 2025 | FLAMES score (machine-learning probability, 0-1) | Pan-trait benchmark across UK Biobank & GWAS Catalog loci | |
2 | Open Targets Platform v25.03 (2025 release notes) | Locus-to-Gene (L2G) score v2 | Gradient-boosting model trained on a hand-curated gold standard; >40 functional-genomics features (QTLs, chromatin, distance) exposed through an open API Open Targets | 6.5 M variants, 2.6 M credible sets, >28 K traits |
3 | Effector Index cited in Turner et al. Cell HGG Advances 2025 | Ei probability (0-1 per gene) | Initial model trained on 12 common diseases with manual curation; emphasises interpretable distance, eQTL and chromatin features; score files downloadable from GitHub PMC | Genome-wide for all RefSeq genes at each GWAS locus |
4 | Schipper et al. “CALDERA” pre-print 2024 | CALDERA score (LASSO-logistic probability) | Uses only 12 biologically interpretable features; truth set constructed with fine-mapped coding signals and corrected for proximity bias medRxiv | 4 764 gene–trait pairs across 19 UKB traits; externally validated |
5 | Lange et al. “Prioritising Parkinson’s disease risk genes…” npj Parkinson’s Dis. 2025 | PoPS rank / score (similarity-based) | >57 000 curated gene features (single-cell RNA-seq, pathways, PPI) merged into a polygenic priority score; benchmarked against PD literature genes Nature | Multi-ancestry PD GWAS; method generalisable genome-wide |
6 | Law et al. “Systematic prioritisation… colorectal cancer risk” Nat Genet 2024 | ABC-MPRA linked-gene score | Curated colon-specific enhancer maps, Micro-C contacts & MPRA validation to assign variant→gene links; publishes per-locus gene lists with confidence tiers Nature | 170 CRC risk loci, 208 effector genes |
New approaches- curated & computational
New approaches- curated & computational
Iterative, more comprehensive
Not available or hosted on lab websites!
Lui et al, 2025
Final consideration- technology
Final consideration- technology