A recent genome-wide association study associated 62 single nucleotide polymorphisms (SNPs) from 43 genomic loci, with fasting lipoprotein subfractions in European–Americans (EAs) at genome-wide levels of significance across three independent samples. Whether these associations are consistent across ethnicities with a non-European ancestry is unknown. We analyzed 15 lipoprotein subfraction measures, on 1677 African–Americans (AAs), 1450 Hispanic–Americans (HAs), and 775 Chinese–Americans (CHN) participating in the multi-ethnic study of atherosclerosis (MESA). Genome-wide data were obtained using the Affymetrix 6.0 and Illumina HumanOmni chips. Linear regression models between genetic variables and lipoprotein subfractions were adjusted for age, gender, body mass index, smoking, study center, and genetic ancestry (based on principal components), and additionally adjusted for Mexican/Non-Mexican status in HAs. A false discovery rate correction was applied separately within the results for each ethnicity to correct for multiple testing. Power calculations revealed that we did not have the power for SNP-based measures of association, so we analyzed phenotype-specific genetic risk scores (GRSs), constructed as in the original genome-wide analysis. We successfully replicated all 15 GRS–lipoprotein associations in 2527 EAs. Among the 15 significant GRS–lipoprotein associations in EAs, 11 were significant in AAs, 13 in HAs, and 1 in CHNs. Further analyses revealed that ethnicity differences could not be explained by differences in linkage disequilibrium, lipid lowering drugs, diabetes, or gender. Our study emphasizes the importance of ethnicity (here indexing genetic ancestry) in genetic risk for CVD and highlights the need to identify ethnicity-specific genetic variants associated with CVD risk.
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This work was supported by the American Heart Association [14BGIA18740011], the United States Department of Agriculture/Agricultural Research Service [CRIS 309-5-001-058] and the National Heart, Lung, and Blood Institute at the National Institutes of Health [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079, UL1-TR-000040, and DK063491]. Funding for SHARe genotyping was provided by NHLBI Contract [N02-HL-64278]. This work is a publication of the USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas and funded in part with federal funds from the USDA/ARS under Cooperative Agreement No. 58-6250-0-008.
The online version of this article (doi: 10.1007/s00439-017-1782-y) contains supplementary material, which is available to authorized users.
Wang, Zhe; Manichukal, Ani; Goff, David C.; Mora, Samia; Ordovas, Jose M.; Pajewski, Nicholas M.; Post, Wendy S.; Rotter, Jerome I.; Sale, Michele M.; Santorico, Stephanie A.; Siscovick, David; Tsai, Michael Y.; Arnett, Donna K.; Rich, Stephen; and Frazier-Wood, Alexis C., "Genetic Associations with Lipoprotein Subfraction Measures Differ by Ethnicity in the Multi-Ethnic Study of Atherosclerosis (MESA)" (2017). Epidemiology Faculty Publications. 51.