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Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits

机译:有条件的GWas汇总统计识别的联合多重sNp分析其它的变化影响复杂性状

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摘要

We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis summary data from the GIANT Consortium for height and body mass index (BMI), with the LD structure estimated from genotype data in two independent cohorts. We identified 36 loci with multiple associated variants for height (38 leading and 49 additional SNPs, 87 in total) via a genome-wide SNP selection procedure. The 49 new SNPs explain approximately 1.3% of variance, nearly doubling the heritability explained at the 36 loci. We did not find any locus showing multiple associated SNPs for BMI. The method we present is computationally fast and is also applicable to case-control data, which we demonstrate in an example from meta-analysis of type 2 diabetes by the DIAGRAM Consortium.
机译:我们提出了一种近似条件和联合关联分析,可以使用来自基因组 - 宽协会研究(GWAS)的概述水平统计和从具有个体级基因型数据的参考样品的估计连接不平衡(LD)。使用此方法,我们分析了来自高度和体重指数(BMI)的巨型财团的Meta分析摘要数据,LD结构从两个独立的队列中的基因型数据估计。我们通过基因组的SNP选择程序识别了36个具有多个相关变体的高度(38个引脚和49个额外的SNP,87个)。 49新的SNP解释了大约1.3%的方差,几乎加倍在36个位置解释的可遗传性。我们没有找到显示BMI的多个关联SNP的轨迹。我们呈现的方法是计算快速的,也适用于案例控制数据,我们在图中由图中的2型糖尿病的示例中演示。

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