Fine-mapping across diverse ancestries drives the discovery of putative causal variants underlying human complex traits and diseases

Genome-wide association studies (GWAS) of human complex traits or diseases often implicate genetic loci that span hundreds or thousands of genetic variants, many of which have similar statistical signi[fi]cance. While statistical fine-mapping in individuals of European descent has made important discoveries, cross-population fine-mapping has the potential to improve power and resolution by capitalizing on the genomic diversity across ancestries. Here we present SuSiEx, an accurate and computationally efficient method for cross-population fine-mapping, which builds on the single-population fine-mapping framework, Sum of Single Effects (SuSiE). SuSiEx integrates data from an arbitrary number of ancestries, explicitly models population-specific allele frequencies and LD patterns, accounts for multiple causal variants in a genomic region, and can be applied to GWAS summary statistics when individual-level data is unavailable. We comprehensively evaluated SuSiEx using simulations, a range of quantitative traits measured in both UK Biobank and Taiwan Biobank, and schizophrenia GWAS across East Asian and European ancestries. In all evaluations, SuSiEx fine-mapped more association signals, produced smaller credible sets and higher posterior inclusion probability (PIP) for putative causal variants, and retained population-specific causal variants.