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" Genetic Architecture of Lipid Traits in Diverse Populations "
Andaleon, Angela
Wheeler, Heather E
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Latin Dissertation
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English
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| Record Number
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1105385
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| Doc. No
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TLpq2308191740
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| Main Entry
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Andaleon, Angela
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Wheeler, Heather E
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| Title & Author
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Genetic Architecture of Lipid Traits in Diverse Populations\ Andaleon, AngelaWheeler, Heather E
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| College
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Loyola University Chicago
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| Date
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2019
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2019
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| Degree
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M.S.
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| Page No
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96
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| Abstract
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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 the 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 association studies (GWAS) and imputed transcriptome-wide association studies in PrediXcan of total cholesterol (CHOL), high-density lipoproteins, triglycerides (TRIG), and low-density lipoproteins in Yoruba in Ibadan, Nigeria (Yoruba, n = 1,251), Filipino in Cebu, Philippines (Cebu, n = 1,799), and Hispanic Americans in the US (HCHS/SoL, n = 11,103). We compared the results to the larger, predominantly European ancestry meta-analysis by the Global Lipids Genetics Consortium (GLGC, n = 196,475) and implicated genetic variants in lipid traits through the regulation of gene expression. Two previously implicated loci met genome-wide significance (P < 5e-8) in our GWAS in Yoruba near CETP and APOE. The top SNP in Cebu associated with TRIG (rs662799, P < 2.7e16) and has been previously implicated in other East Asian studies. We show rs662799 may also be involved in the long-distance regulation of BACE1 and SIDT2 with increased predicted expression significantly associating (FDR < 0.05) with lower TRIG in both genes. Our novel BACE1 and SIDT2 findings were replicated using summary statistics from GLGC. Our GWAS in HCHS/SoL found 29 significant independent loci and 2 of the loci for CHOL have minor allele frequency < 0.01. After performing PrediXcan in in HCHS/SoL, we found 59 significant gene-tissue-phenotype associations (P < 3.61e-8) with 14 unique significant genes, many of which occurred across multiple phenotypes, tissues, and ethnicities and replicated in GLGC (44/59) and 3,855 individuals from diverse ancestries in the Multi-Ethnic Study of Atherosclerosis (45/59). These include lipid genes such as SORT1, CETP, and PSRC1 and genes implicated in cardiovascular phenotypes, such as CCL22 and ICAM1. The majority (40/59) of significant associations colocalized with expression quantitative trait loci, 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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Bioinformatics
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Biostatistics
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Genetics
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