Variants for HDL-C, LDL-C, and triglycerides identified from admixture mapping and fine-mapping analysis in African American families.

TitleVariants for HDL-C, LDL-C, and triglycerides identified from admixture mapping and fine-mapping analysis in African American families.
Publication TypeJournal Article
Year of Publication2015
AuthorsShetty, PB, Tang, H, Feng, T, Tayo, B, Morrison, AC, Kardia, SLR, Hanis, CL, Arnett, DK, Hunt, SC, Boerwinkle, E, Rao, DC, Cooper, RS, Risch, N, Zhu, X
Corporate Authors
JournalCirc Cardiovasc Genet
Volume8
Issue1
Pagination106-13
Date Published2015 Feb
ISSN1942-3268
KeywordsAdult, African Americans, Aged, Aged, 80 and over, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Chromosome Mapping, Chromosomes, Human, Family, Female, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Triglycerides
Abstract

BACKGROUND: Admixture mapping of lipids was followed-up by family-based association analysis to identify variants for cardiovascular disease in African Americans.

METHODS AND RESULTS: The present study conducted admixture mapping analysis for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. The analysis was performed in 1905 unrelated African American subjects from the National Heart, Lung and Blood Institute's Family Blood Pressure Program (FBPP). Regions showing admixture evidence were followed-up with family-based association analysis in 3556 African American subjects from the FBPP. The admixture mapping and family-based association analyses were adjusted for age, age(2), sex, body mass index, and genome-wide mean ancestry to minimize the confounding caused by population stratification. Regions that were suggestive of local ancestry association evidence were found on chromosomes 7 (low-density lipoprotein cholesterol), 8 (high-density lipoprotein cholesterol), 14 (triglycerides), and 19 (total cholesterol and triglycerides). In the fine-mapping analysis, 52 939 single-nucleotide polymorphisms (SNPs) were tested and 11 SNPs (8 independent SNPs) showed nominal significant association with high-density lipoprotein cholesterol (2 SNPs), low-density lipoprotein cholesterol (4 SNPs), and triglycerides (5 SNPs). The family data were used in the fine-mapping to identify SNPs that showed novel associations with lipids and regions, including genes with known associations for cardiovascular disease.

CONCLUSIONS: This study identified regions on chromosomes 7, 8, 14, and 19 and 11 SNPs from the fine-mapping analysis that were associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides for further studies of cardiovascular disease in African Americans.

DOI10.1161/CIRCGENETICS.114.000481
Alternate JournalCirc Cardiovasc Genet
PubMed ID25552592
PubMed Central IDPMC4378661
Grant ListHL007567-29 / HL / NHLBI NIH HHS / United States
HL086718 / HL / NHLBI NIH HHS / United States
R01 GM073059 / GM / NIGMS NIH HHS / United States
R01 HG003054 / HG / NHGRI NIH HHS / United States
R01 HL086718 / HL / NHLBI NIH HHS / United States
RR03655 / RR / NCRR NIH HHS / United States
T32 HL007567 / HL / NHLBI NIH HHS / United States