Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes.
Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes.
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DOI：
10.1038/ncomms10531
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发表时间：
2016-01-28
影响因子：
16.6
通讯作者：
Kadowaki T
中科院分区：
文献类型：
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作者：
Imamura M;Takahashi A;Yamauchi T;Hara K;Yasuda K;Grarup N;Zhao W;Wang X;Huerta-Chagoya A;Hu C;Moon S;Long J;Kwak SH;Rasheed A;Saxena R;Ma RC;Okada Y;Iwata M;Hosoe J;Shojima N;Iwasaki M;Fujita H;Suzuki K;Danesh J;Jørgensen T;Jørgensen ME;Witte DR;Brandslund I;Christensen C;Hansen T;Mercader JM;Flannick J;Moreno-Macías H;Burtt NP;Zhang R;Kim YJ;Zheng W;Singh JR;Tam CH;Hirose H;Maegawa H;Ito C;Kaku K;Watada H;Tanaka Y;Tobe K;Kawamori R;Kubo M;Cho YS;Chan JC;Sanghera D;Frossard P;Park KS;Shu XO;Kim BJ;Florez JC;Tusié-Luna T;Jia W;Tai ES;Pedersen O;Saleheen D;Maeda S;Kadowaki T
全基因组关联研究（GWAS）已确定了80多个2型糖尿病（T2 D）易感基因座，但其大部分遗传性仍有待阐明。在本研究中，我们对日本人群中T2D的GWAS进行了荟萃分析。来自发现和后续验证分析的组合数据（23，399例T2D病例和31，722例对照）确定了7个具有全基因组意义的新基因座（P<5 × 10−8），rs1116357靠近CCDC 85 A，rs147538848在FAM 60 A，rs1575972靠近DMRTA 1，rs9309245靠近ASB 3，rs67156297靠近ATP 8B2，MIR4686附近的rs7107784和INAFM2附近的rs67839313。其中，4个基因座与T2D的关联在除日本人以外的多种族人群中重复（高达65，936例T2D和158，030例对照，P<0.007）。这些结果表明，扩大单一种族GWAS仍然是有用的，以确定新的易感基因座复杂的性状，不仅为种族特异性基因座，但也为共同的基因座在不同的种族。在这里，Imamura等人进行了全基因组关联研究的荟萃分析，以确定日本人群中2型糖尿病（T2D）的新易感基因座。通过这样做，这项研究表明，种族特异性和种族共享的遗传基因座都可能导致T2D风险。
Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 × 10−8), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities. Here, Imamura et al. conduct meta-analysis of genome-wide association studies to identify novel susceptibility loci for type 2 diabetes (T2D) in the Japanese population. By doing so, this study shows that both ethnicity-specific and ethnically-shared genetic loci can contribute to T2D risk.