College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, People's Republic of China.
Department of Management Information Systems, Terry College of Business, University of Georgia, Athens, Georgia, USA.
Sci Rep. 2019 Jul 17;9(1):10340. doi: 10.1038/s41598-019-46808-2.
Plenty of genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms (SNPs) for coronary artery disease (CAD) and blood pressure (BP). However, these SNPs only explain a small proportion of the heritability of two traits/diseases. Although high BP is a major risk factor for CAD, the genetic intercommunity between them remain largely unknown. To recognize novel loci associated with CAD and BP, a genetic-pleiotropy-informed conditional false discovery rate (cFDR) method was applied on two summary statistics of CAD and BP from existing GWASs. Stratified Q-Q and fold enrichment plots showed a high pleiotropic enrichment of SNPs associated with two traits. Adopting a cFDR of 0.05 as a threshold, 55 CAD-associated loci (25 variants being novel) and 47 BP loci (18 variants being novel) were identified, 25 of which were pleiotropic loci (13 variants being novel) for both traits. Among the 32 genes these 25 SNPs were annotated to, 20 genes were newly detected compared to previous GWASs. This study showed the cFDR approach could improve gene discovery by incorporating GWAS datasets of two related traits. These findings may provide novel understanding of etiology relationships between CAD and BP.
大量全基因组关联研究（GWAS）已经确定了许多与冠心病（CAD）和血压（BP）相关的单核苷酸多态性（SNPs）。然而，这些 SNP 仅解释了两个特征/疾病遗传率的一小部分。虽然高血压是 CAD 的主要危险因素，但它们之间的遗传联系在很大程度上仍不清楚。为了识别与 CAD 和 BP 相关的新基因座，应用一种遗传多效性信息条件假发现率（cFDR）方法，对两个现有 GWAS 的 CAD 和 BP 的两个汇总统计数据进行分析。分层 Q-Q 和折叠富集图显示，与两个特征相关的 SNP 存在高度的多效性富集。采用 cFDR 为 0.05 作为阈值，鉴定出 55 个与 CAD 相关的基因座（25 个变体是新的）和 47 个与 BP 相关的基因座（18 个变体是新的），其中 25 个是与两个特征相关的多效性基因座（13 个变体是新的）。在这 25 个 SNP 注释的 32 个基因中，有 20 个基因是以前的 GWAS 中未检测到的。本研究表明，通过整合两个相关特征的 GWAS 数据集，cFDR 方法可以提高基因发现的效率。这些发现可能为 CAD 和 BP 之间的病因关系提供新的认识。
