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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  CETP  associated with HDL cholesterol ( P  = 9.0 × 10 −10 ) and  rs1065853  upstream of  APOE  associated with LDL cholesterol ( P  = 6.6 × 10 −9 ). The top SNP in the Filipino cohort associated with triglyceride levels ( rs662799 ;  P  = 2.7 × 10 −16 ) and has been previously implicated in other East Asian studies. While this SNP is located directly upstream of well known  APOA5 , we show it may also be involved in the regulation of  BACE1  and  SIDT2 . Our gene-based association analysis, PrediXcan, revealed decreased expression of  BACE1  and decreased expression of  SIDT2  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  BACE1  and  SIDT2  findings were confirmed using summary statistics from the Global Lipids Genetic Consortium (GLGC) meta-GWAS.

Gene-based association study for lipid traits in diverse cohorts implicates BACE1 and SIDT2 regulation in triglyceride levels