Gene-based association study for lipid traits in diverse cohorts implicates and regulation in triglyceride levels. Journal Article

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Authors: Andaleon, A; Mogil, LS; Wheeler, HE
Article Title: Gene-based association study for lipid traits in diverse cohorts implicates and regulation in triglyceride levels.
Abstract: Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted on lipid genetics, they mainly focus on Europeans and thus their transferability to diverse populations is unclear. We performed SNP- and gene-level genome-wide association studies (GWAS) of four lipid traits in cohorts from Nigeria and the Philippines and compared them to the results of larger, predominantly European meta-analyses. Two previously implicated loci met genome-wide significance in our SNP-level GWAS in the Nigerian cohort, rs34065661 in associated with HDL cholesterol ( = 9.0 × 10) and rs1065853 upstream of associated with LDL cholesterol ( = 6.6 × 10). The top SNP in the Filipino cohort associated with triglyceride levels (rs662799;  = 2.7 × 10) and has been previously implicated in other East Asian studies. While this SNP is located directly upstream of well known , we show it may also be involved in the regulation of and . Our gene-based association analysis, PrediXcan, revealed decreased expression of and decreased expression of in several tissues, all driven by rs662799, significantly associate with increased triglyceride levels in Filipinos (FDR 0.1). In addition, our PrediXcan analysis implicated gene regulation as the mechanism underlying the associations of many other previously discovered lipid loci. Our novel and findings were confirmed using summary statistics from the Global Lipids Genetic Consortium (GLGC) meta-GWAS.
Journal Title: PeerJ
ISSN: 2167-8359
Publisher: Unknown  
Date Published: 2018