Genome-wide association study identifies 112 new loci for body mass index in the Japanese population
Genome-wide association study identifies 112 new loci for body mass index in the Japanese population
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DOI：
10.1038/ng.3951
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发表时间：
2017-10-01
期刊：
影响因子：
30.8
通讯作者：
Kamatani, Yoichiro
中科院分区：
文献类型：
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作者：
Akiyama, Masato;Okada, Yukinori;Kamatani, Yoichiro
肥胖是一个危险因素，为各种各样的健康问题。在日本人（n = 173，430）的体重指数（BMI）的全基因组关联研究（GWAS）中，我们发现85个位点与肥胖显著相关（P < 5.0 x 10（-8）），其中51个以前未知。我们通过将这些结果与欧洲GWAS的结果整合进行了跨祖先荟萃分析，并确定了61个新的基因座。总的来说，这项研究确定了112个新的基因座，使以前已知的BMI相关基因座的数量增加了一倍。通过用细胞类型特异性调节标记注释相关变体，我们发现了CD 19（+）细胞中变体的富集。我们还发现BMI与淋巴细胞计数（P = 6.46 × 10（-5），r（g）= 0.18）以及BMI与多种复杂疾病之间存在显著的遗传相关性。这些发现提供了淋巴细胞与体重调节相关的遗传证据，并为肥胖的发病机制提供了见解。
Obesity is a risk factor for a wide variety of health problems. In a genome-wide association study (GWAS) of body mass index (BMI) in Japanese people (n = 173,430), we found 85 loci significantly associated with obesity (P < 5.0 x 10(-8)), of which 51 were previously unknown. We conducted trans-ancestral meta-analyses by integrating these results with the results from a GWAS of Europeans and identified 61 additional new loci. In total, this study identifies 112 novel loci, doubling the number of previously known BMI-associated loci. By annotating associated variants with cell-type-specific regulatory marks, we found enrichment of variants in CD19(+) cells. We also found significant genetic correlations between BMI and lymphocyte count (P = 6.46 x 10(-5), r(g) = 0.18) and between BMI and multiple complex diseases. These findings provide genetic evidence that lymphocytes are relevant to body weight regulation and offer insights into the pathogenesis of obesity.