Large scale genome-wide association study in a Japanese population identified 45 novel susceptibility loci for 22 diseases
Large scale genome-wide association study in a Japanese population identified 45 novel susceptibility loci for 22 diseases
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DOI：
10.1101/795948
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发表时间：
2019-10
期刊：
影响因子：
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通讯作者：
K. Ishigaki;M. Akiyama;M. Kanai;A. Takahashi;Eiryo Kawakami;Hiroki Sugishita;S. Sakaue;N. Matoba;Siew-Kee Low;Y. Okada;C. Terao;T. Amariuta;S. Gazal;Y. Kochi;M. Horikoshi;Ken Suzuki;K. Ito;Y. Momozawa;M. Hirata;K. Matsuda;M. Ikeda;N. Iwata;S. Ikegawa;I. Kou;Toshihiro Tanaka;H. Nakagawa;A. Suzuki;T. Hirota;M. Tamari;K. Chayama;D. Miki;Masaki Mori;S. Nagayama;Y. Daigo;Y. Miki;T. Katagiri;O. Ogawa;W. Obara;Hidemi Ito;Teruhiko Yoshida;I. Imoto;Takashi Takahashi;C. Tanikawa;Takao Suzuki;N. Sinozaki;S. Minami;H. Yamaguchi;S. Asai;Yasuo Takahashi;K. Yamaji;Kazuhisa Takahashi;T. Fujioka;R. Takata;H. Yanai;A. Masumoto;Y. Koretsune;H. Kutsumi;M. Higashiyama;S. Murayama;N. Minegishi;Kichiya Suzuki;K. Tanno;A. Shimizu;T. Yamaji;M. Iwasaki;N. Sawada;H. Uemura;Keitaro Tanaka;M. Naito;Makoto Sasaki;K. Wakai;S. Tsugane;Masayuki Yamamoto;Kazuhiko Yamamoto;Yoshinori Murakami;Yusuke Nakamura;S. Raychaudhuri;J. Inazawa;T. Yamauchi;T. Kadowaki;M. Kubo;Y. Kamatani
中科院分区：
文献类型：
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作者：
K. Ishigaki;M. Akiyama;M. Kanai;A. Takahashi;Eiryo Kawakami;Hiroki Sugishita;S. Sakaue;N. Matoba;Siew-Kee Low;Y. Okada;C. Terao;T. Amariuta;S. Gazal;Y. Kochi;M. Horikoshi;Ken Suzuki;K. Ito;Y. Momozawa;M. Hirata;K. Matsuda;M. Ikeda;N. Iwata;S. Ikegawa;I. Kou;Toshihiro Tanaka;H. Nakagawa;A. Suzuki;T. Hirota;M. Tamari;K. Chayama;D. Miki;Masaki Mori;S. Nagayama;Y. Daigo;Y. Miki;T. Katagiri;O. Ogawa;W. Obara;Hidemi Ito;Teruhiko Yoshida;I. Imoto;Takashi Takahashi;C. Tanikawa;Takao Suzuki;N. Sinozaki;S. Minami;H. Yamaguchi;S. Asai;Yasuo Takahashi;K. Yamaji;Kazuhisa Takahashi;T. Fujioka;R. Takata;H. Yanai;A. Masumoto;Y. Koretsune;H. Kutsumi;M. Higashiyama;S. Murayama;N. Minegishi;Kichiya Suzuki;K. Tanno;A. Shimizu;T. Yamaji;M. Iwasaki;N. Sawada;H. Uemura;Keitaro Tanaka;M. Naito;Makoto Sasaki;K. Wakai;S. Tsugane;Masayuki Yamamoto;Kazuhiko Yamamoto;Yoshinori Murakami;Yusuke Nakamura;S. Raychaudhuri;J. Inazawa;T. Yamauchi;T. Kadowaki;M. Kubo;Y. Kamatani
当前遗传学研究的绝大多数参与者都有欧洲血统1-3，这限制了我们对非欧洲人群复杂疾病的遗传学理解。为了解决这个问题，我们的目标是通过对 212,453 名日本人进行全基因组关联研究 (GWAS)，涵盖 42 种疾病，阐明东亚人群的多基因疾病生物学。我们在 30 种疾病的 331 个基因座中检测到 383 个独立信号，其中 45 个基因座是新的（P < 0.6），具有错义变异，这些变异在欧洲人群（千人基因组计划）中是单态的，包括与冠状动脉疾病相关的 rs11235604（自噬相关基因 ATG16L2 的 p.R220W）。我们进一步研究了全基因组转录因子占据的 2,868 个注释中的遗传性富集，并在 9 种疾病 (FDR < 0.05) 中鉴定了 378 个显着富集（例如免疫相关疾病的 NF-κB）。在日本人群中进行的大规模 GWAS 提供了对常见复杂疾病病因学的见解，并强调了在非欧洲人群中进行 GWAS 的重要性。
The 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 383 independent signals in 331 loci for 30 diseases, among which 45 loci were novel (P 0.6) with missense variants which are monomorphic in European populations (1000 Genomes Project) including rs11235604(p.R220W of ATG16L2, a autophagy-related gene) associated with coronary artery disease. We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, andidentified 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.