A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations

作者：Imamura Minako; Maeda Shiro^*; Yamauchi Toshimasa; Hara Kazuo; Yasuda Kazuki; Morizono Takashi; Takahashi Atsushi; Horikoshi Momoko; Nakamura Masahiro; Fujita Hayato; Tsunoda Tatsuhiko; Kubo Michiaki; Watada Hirotaka; Maegawa Hiroshi; Okada Iwabu Miki; Iwabu Masato; Shojima Nobuhiro; Ohshige Toshihiko; Omori Shintaro; Iwata Minoru; Hirose Hiroshi; Kaku Kohei; Ito Chikako; Tanaka Yasushi; Tobe Kazuyuki; Kashiwagi Atsunori; Kawamori Ryuzo; Kasuga Masato

来源：Human Molecular Genetics, 2012, 21(13): 3042-3049.

DOI：10.1093/hmg/dds113

To identify a novel susceptibility locus for type 2 diabetes, we performed an imputation-based, genome-wide association study (GWAS) in a Japanese population using newly obtained imputed-genotype data for 2 229 890 single-nucleotide polymorphisms (SNPs) estimated from previously reported, directly genotyped GWAS data in the same samples (stage 1: 4470 type 2 diabetes versus 3071 controls). We directly genotyped 43 new SNPs with P-values of 10(4) in a part of stage-1 samples (2692 type 2 diabetes versus 3071 controls), and the associations of validated SNPs were evaluated in another 11 139 Japanese individuals (stage 2: 7605 type 2 diabetes versus 3534 controls). Combined meta-analysis using directly genotyped data for stages 1 and 2 revealed that rs515071 in ANK1 and rs7656416 near MGC21675 were associated with type 2 diabetes in the Japanese population at the genome-wide significant level (P 5 10(8)). The association of rs515071 was also observed in European GWAS data (combined P for all populations 6.14 10(10)). Rs7656416 was in linkage disequilibrium to rs6815464, which had recently been identified as a top signal in a meta-analysis of East Asian GWAS for type 2 diabetes (r(2) 0.76 in stage 2). The association of rs7656416 with type 2 diabetes disappeared after conditioning on rs6815464. These results indicate that the ANK1 locus is a new, common susceptibility locus for type 2 diabetes across different ethnic groups. The signal of association was weaker in the directly genotyped data, so the improvement in signal indicates the importance of imputation in this particular case.

• 出版日期2012-7-1
• 单位河北医科大学