由跨种族样本组成的大规模GWAS荟萃分析确定了BMI的各种遗传信号

Yiyun Chen, Zhenxiao Xu, An-Di Zhao
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摘要

由于计算能力和统计理论的发展,全基因组关联研究(Genome-wide association studies, GWAS)不断得到改进,以获得更高的准确度和更低的偏倚。GWAS在不同人群(如欧洲血统或亚洲人群)中确定了数百个体重指数易感位点。荟萃分析使我们能够整合各种研究的统计结果,以发现更多的GWAS遗传信号,并发现顺性或跨种族群体的不同信号。在这里,我们结合了来自三个大规模遗传学研究来源的数据:英国生物银行、GIANT财团和一项著名的日本研究。在200多万个候选snp中,经Bonferroni校正(P < 2.5*10^-8),我们成功检测到686个显著snp,其中大部分是以前检测到的。排名前五的snp分别是:“rs1558902”(P值= 2.394*10^-36)、“rs1421085”(P值= 4.152*10^-36)、“rs2237897”(P值= 2.542*10^-32)、“rs2237896”(P值= 3.966*10^-32)、“rs7202116”(P值= 2.702*10^-31)。虽然荟萃分析确定的变异总数低于日本基于人群的关联研究,但荟萃分析成功地确定了几个未被单组关联研究捕获的新位点。我们还挖掘了原始汇总统计数据集,并对不同人群的统计结果分别进行了分析比较。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Large-scale GWAS meta-analysis consisting of trans-ethnic samples identifies various genetic signals on BMI
Due to the development of computational power and statistical theories, Genome-wide association studies (GWAS) have constantly been improved to gain higher power with reduced bias. GWAS identify hundreds of susceptibility loci body mass index in various populations such as European-ancestry, or Asian groups. Meta-analysis enables us to incorporate statistical results from various studies to detect more genetics signals in GWAS, as well as discover different signals from cis- or trans-ethnic groups. Here we combined data from three sources of large-scale genetics studies: UK Biobank, GIANT consortium, and a famous Japanese study. Among over two million candidate SNPs, we successfully detected 686 significant SNPs after Bonferroni correction (P < 2.5*10^-8), with most of them being detected previously. The top five SNPs are: “rs1558902” (P value = 2.394*10^-36), “rs1421085” (P value = 4.152*10^-36), “rs2237897” (P value = 2.542*10^-32), “rs2237896” (P value = 3.966*10^-32), “rs7202116” (P value = 2.702*10^-31). Although the total number of variants identified by the meta-analysis is lower than the Japanese population-based association study, meta-analysis successfully identifies several new loci not captured by the single-group association study. We also explored the original summary statistics datasets and conducted analysis to compare the statistical results from different populations separately.
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