Pan-UK Biobank GWAS improves discovery, analysis of genetic architecture, and resolution into ancestry-enriched effects

Abstract

SummaryLarge biobanks, such as the UK Biobank (UKB), enable massive phenome by genome-wide association studies that elucidate genetic etiology of complex traits. However, individuals from diverse genetic ancestry groups are often excluded from association analyses due to concerns about population structure introducing false positive associations. Here, we generate mixed model associations and meta-analyses across genetic ancestry groups, inclusive of a larger fraction of the UKB than previous efforts, to produce freely-available summary statistics for 7,271 traits. We build a quality control and analysis framework informed by genetic architecture. Overall, we identify 14,676 significant loci in the meta-analysis that were not found in the European genetic ancestry group alone, including novel associations for example betweenCAMK2Dand triglycerides. We also highlight associations from ancestry-enriched variation, including a known pleiotropic missense variant inG6PDassociated with several biomarker traits. We release these results publicly alongside FAQs that describe caveats for interpretation of results, enhancing available resources for interpretation of risk variants across diverse populations.