Genetically regulated gene expression underlies lipid traits in Hispanic cohorts release_yzwp2bblq5hobgfrxvrrnyelam

Abstract

Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted in genetic variation underlying lipid levels, they mainly comprise individuals of European ancestry and thus their transferability to non-European populations is unclear. We performed genome-wide (GWAS) and imputed transcriptome-wide association studies of four lipid traits in the Hispanic Community Health Study/Study of Latinos cohort (HCHS/SoL, n = 11,103), replicated in the Multi-Ethnic Study of Atherosclerosis (MESA, n = 3,855), and compared the results to the larger, predominantly European ancestry meta-analysis by the Global Lipids Genetics Consortium (GLGC, n = 196,475). GWAS revealed SNPs in regions within or near known lipid and admixture mapping did not find significant associations between local ancestry and lipid phenotypes. In the imputed transcriptome-wide association study in multiple tissues and in different ethnicities, we found 59 significant gene-tissue-phenotype associations (P &lt; 3.61 x 10<jats:sup>-8</jats:sup>) with 14 unique significant genes, many of which occurred across multiple phenotypes, tissues, and ethnicities and replicated in MESA (45/59) and in GLGC (44/59). These include well-studied lipid genes such as <jats:italic>SORT1</jats:italic>, <jats:italic>CETP</jats:italic>, and <jats:italic>PSRC1</jats:italic>, as well as genes that have been implicated in cardiovascular phenotypes, such as <jats:italic>CCL22</jats:italic> and <jats:italic>ICAM1</jats:italic>. The majority (40/59) of significant associations colocalized with expression quantitative trait loci (eQTLs), indicating a possible mechanism of gene regulation in lipid level variation. To fully characterize the genetic architecture of lipid traits in diverse populations, larger studies in non-European ancestry populations are needed.
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