Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases
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- 8 June 2020
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 52 (7), 669-679
- https://doi.org/10.1038/s41588-020-0640-3
Abstract
The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.58 × 10−9). East Asian–specific missense variants were identified as candidate causal variants for three novel loci, and we successfully replicated two of them by analyzing independent Japanese cohorts; p.R220W of ATG16L2 (associated with coronary artery disease) and p.V326A of POT1 (associated with lung cancer). We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, and identified 378 significant enrichments across nine diseases (false discovery rate < 0.05) (for example, NKX3-1 for prostate cancer). This large-scale GWAS in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.Keywords
Funding Information
- Japan Agency for Medical Research and Development (JP20dk0207045, JP18kk0205009, JP19ek0210081, JP16ck0106096, JP17km0305001, JP19km0105001, JP19km0105002, JP17km0305002)
- National Cancer Center Research and Development Fund
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