Department of Biostatistics, Harvard School of Public Health Boston, MA, USA.
Front Genet. 2013 May 31;4:103. doi: 10.3389/fgene.2013.00103. eCollection 2013.
Increasing evidence suggests that single nucleotide polymorphisms (SNPs) associated with complex traits are more likely to be expression quantitative trait loci (eQTLs). Incorporating eQTL information hence has potential to increase power of genome-wide association studies (GWAS). In this paper, we propose using eQTL weights as prior information in SNP based association tests to improve test power while maintaining control of the family-wise error rate (FWER) or the false discovery rate (FDR). We apply the proposed methods to the analysis of a GWAS for childhood asthma consisting of 1296 unrelated individuals with German ancestry. The results confirm that eQTLs are enriched for previously reported asthma SNPs. We also find that some SNPs are insignificant using procedures without eQTL weighting, but become significant using eQTL-weighted Bonferroni or Benjamini-Hochberg procedures, while controlling the same FWER or FDR level. Some of these SNPs have been reported by independent studies in recent literature. The results suggest that the eQTL-weighted procedures provide a promising approach for improving power of GWAS. We also report the results of our methods applied to the large-scale European GABRIEL consortium data.
越来越多的证据表明，与复杂性状相关的单核苷酸多态性（SNP）更有可能成为表达数量性状基因座（eQTL）。因此，纳入 eQTL 信息有可能提高全基因组关联研究（GWAS）的效力。在本文中，我们提出在基于 SNP 的关联检验中使用 eQTL 权重作为先验信息，以在保持家族错误率（FWER）或假发现率（FDR）控制的情况下提高检验效力。我们将提出的方法应用于一项包含 1296 名无亲缘关系的德国血统儿童哮喘 GWAS 的分析中。结果证实，eQTL 富集了先前报道的哮喘 SNP。我们还发现，一些 SNP 在不使用 eQTL 加权的程序中不显著，但在使用 eQTL 加权的 Bonferroni 或 Benjamini-Hochberg 程序时变得显著，同时控制相同的 FWER 或 FDR 水平。其中一些 SNP 已被最近文献中的独立研究报道过。结果表明，eQTL 加权程序为提高 GWAS 的效力提供了一种有前途的方法。我们还报告了我们的方法应用于大型欧洲 GABRIEL 联盟数据的结果。
