Ishigaki, KazuyoshiAkiyama, MasatoKanai, MasahiroTakahashi, AtsushiKawakami, EiryoSugishita, HirokiSakaue, SaoriMatoba, NanaLow, Siew-KeeOkada, YukinoriTerao, ChikashiAmariuta, TiffanyGazal, StevenKochi, YutaHorikoshi, MomokoSuzuki, KenIto, KaoruKoyama, SatoshiOzaki, KouichiNiida, ShumpeiSakata, YasushiSakata, YasuhikoKohno, TakashiShiraishi, KouyaMomozawa, YukihideHirata, MakotoMatsuda, KoichiIkeda, MasashiIwata, NakaoIkegawa, ShiroKou, IkuyoTanaka, ToshihiroNakagawa, HidewakiSuzuki, AkariHirota, TomomitsuTamari, MayumiChayama, KazuakiMiki, DaikiMori, MasakiNagayama, SatoshiDaigo, YataroMiki, YoshioKatagiri, ToyomasaOgawa, OsamuObara, WataruIto, HidemiYoshida, TeruhikoImoto, IsseiTakahashi, TakashiTanikawa, ChizuSuzuki, TakaoSinozaki, NobuakiMinami, ShiroYamaguchi, HirokiAsai, SatoshiTakahashi, YasuoYamaji, KenTakahashi, KazuhisaFujioka, TomoakiTakata, RyoYanai, HidekiMasumoto, AkihideKoretsune, YukihiroKutsumi, HiromuHigashiyama, MasahikoMurayama, ShigeoMinegishi, NaokoSuzuki, KichiyaTanno, KozoShimizu, AtsushiYamaji, TaikiIwasaki, MotokiSawada, NorieUemura, HirokazuTanaka, KeitaroNaito, MarikoSasaki, MakotoWakai, KenjiTsugane, ShoichiroYamamoto, MasayukiYamamoto, KazuhikoMurakami, YoshinoriNakamura, YusukeRaychaudhuri, SoumyaInazawa, JohjiYamauchi, ToshimasaKadowaki, TakashiKubo, MichiakiKamatani, Yoichiro2023-12-132020-06-08Ishigaki, Kazuyoshi, Masato Akiyama, Masahiro Kanai, Atsushi Takahashi, Eiryo Kawakami, Hiroki Sugishita, Saori Sakaue et al. "Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases." Nat Genet 52, no. 7 (2020): 669-679. DOI: 10.1038/s41588-020-0640-31061-40361546-1718https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37377513The overwhelming majority of participants in current genetic studies are of European ancestry1–3, limiting our genetic understanding of complex disease in non-European populations. To address this, we aimed to elucidate polygenic disease biology in the East Asian population by conducting 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, among which 25 loci were novel (P < 9.58 x 10-9, an empirically estimated significance threshold). 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 (FDR < 0.05) (e.g. NF-κB for immune-related diseases). This large-scale GWAS in a Japanese population provides insights into the etiology of common complex diseases and highlights the importance of performing GWAS in non-European populations.en-USGeneticsJournal Article2023-12-1310.1038/s41588-020-0640-3