@article{5328bd3f9c074ff59aada5a5172aff77,
title = "Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population",
abstract = " To understand the genetics of type 2 diabetes in people of Japanese ancestry, we conducted A meta-analysis of four genome-wide association studies (GWAS; 36,614 cases and 155,150 controls of Japanese ancestry). We identified 88 type 2 diabetes–associated loci (P < 5.0 × 10 −8 ) with 115 independent signals (P < 5.0 × 10 −6 ), of which 28 loci with 30 signals were novel. Twenty-eight missense variants were in linkage disequilibrium (r 2 > 0.6) with the lead variants. Among the 28 missense variants, three previously unreported variants had distinct minor allele frequency (MAF) spectra between people of Japanese and European ancestry (MAF JPN > 0.05 versus MAF EUR < 0.01), including missense variants in genes related to pancreatic acinar cells (GP2) and insulin secretion (GLP1R). Transethnic comparisons of the molecular pathways identified from the GWAS results highlight both ethnically shared and heterogeneous effects of a series of pathways on type 2 diabetes (for example, monogenic diabetes and beta cells).",
author = "Ken Suzuki and Masato Akiyama and Kazuyoshi Ishigaki and Masahiro Kanai and Jun Hosoe and Nobuhiro Shojima and Atsushi Hozawa and Aya Kadota and Kiyonori Kuriki and Mariko Naito and Kozo Tanno and Yasushi Ishigaki and Makoto Hirata and Koichi Matsuda and Nakao Iwata and Masashi Ikeda and Norie Sawada and Taiki Yamaji and Motoki Iwasaki and Shiro Ikegawa and Shiro Maeda and Yoshinori Murakami and Kenji Wakai and Shoichiro Tsugane and Makoto Sasaki and Masayuki Yamamoto and Yukinori Okada and Michiaki Kubo and Yoichiro Kamatani and Momoko Horikoshi and Toshimasa Yamauchi and Takashi Kadowaki",
note = "Funding Information: We acknowledge the staff of the BBJ Project, IMM, ToMMo, the JPHC Study and the J-MICC Study for their outstanding assistance in collecting samples and clinical information. We also acknowledge the members of the Genetic Study Group of the Investigation Committee on the Ossification of Spinal Ligaments for recruiting subjects to the ossification of the posterior longitudinal ligament GWAS used in this study, which was supported by the Japan Agency for Medical Research and Development (AMED) (17ek0109223h0001) (S.I.). The study of psychiatric disorders was supported by AMED under grants JP18dm0107097 (N.I., M. Ikeda and K.Y.), JP18km0405201 (N.I.) and JP18km0405208 (M. Ikeda). We are grateful to members of The Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study. This research was funded by the Tailor-Made Medical Treatment Program (the BBJ Project) of the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) and AMED (M. Kubo and Y.M.). This research was also supported by the Advanced Genome Research and Bioinformatics Study to Facilitate Medical Innovation (GRIFIN) in the Platform Program for Promotion of Genome Medicine (P3GM) of AMED (T.K.), JP18km0405202. IMM is supported by MEXT and AMED (grants JP18km0105003 and JP18km0105004, M.S.) ToMMo is supported by MEXT and AMED (grants JP18km0105001, JP18km0105002, JP18km0405203 and JP18km0405001, M.Y.). The JPHC Study has been supported by the National Cancer Center Research and Development Fund since 2011 and was supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan from 1989 to 2010 (S.T.). The J-MICC Study was supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer (17015018) and Innovative Areas (221S0001) and the JSPS KAKENHI Grant (16H06277) from MEXT (A.K., K.K., M.N. and K.W.). Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2019",
month = mar,
day = "1",
doi = "10.1038/s41588-018-0332-4",
language = "English",
volume = "51",
pages = "379--386",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",
}
