Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population

Ken Suzuki, Masato Akiyama, Kazuyoshi Ishigaki, Masahiro Kanai, Jun Hosoe, Nobuhiro Shojima, Atsushi Hozawa, Aya Kadota, Kiyonori Kuriki, Mariko Naito, Kozo Tanno, Yasushi Ishigaki, Makoto Hirata, Koichi Matsuda, Nakao Iwata, Masashi Ikeda, Norie Sawada, Taiki Yamaji, Motoki Iwasaki, Shiro IkegawaShiro Maeda, Yoshinori Murakami, Kenji Wakai, Shoichiro Tsugane, Makoto Sasaki, Masayuki Yamamoto, Yukinori Okada, Michiaki Kubo, Yoichiro Kamatani, Momoko Horikoshi, Toshimasa Yamauchi, Takashi Kadowaki

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13 Citations (Scopus)

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).

Original languageEnglish
Pages (from-to)379-386
Number of pages8
JournalNature Genetics
Volume51
Issue number3
DOIs
Publication statusPublished - 01-03-2019

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All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Suzuki, K., Akiyama, M., Ishigaki, K., Kanai, M., Hosoe, J., Shojima, N., Hozawa, A., Kadota, A., Kuriki, K., Naito, M., Tanno, K., Ishigaki, Y., Hirata, M., Matsuda, K., Iwata, N., Ikeda, M., Sawada, N., Yamaji, T., Iwasaki, M., ... Kadowaki, T. (2019). Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population. Nature Genetics, 51(3), 379-386. https://doi.org/10.1038/s41588-018-0332-4