Document Type

Article

Publication Date

1-29-2018

Publication Title

PeerJ

Volume

6

Pages

1- 27

Publisher Name

PeerJ

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 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 BACE 1and 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 BACE1 and SIDT2 findings were confirmed using summary statistics from the Global Lipids Genetic Consortium (GLGC) meta-GWAS.

Identifier

29404214

Comments

Author Posting. © The Authors 2018. This article is posted here for personal use, not for redistribution. The article was published in PeerJ, 2018, https://doi.org/10.7717/peerj.4314

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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