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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
Secondary AuthorsZhu X
Corporate AuthorsCandidate Gene Association Resource(CARe) Consortium
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 ListN01HC55020 / HL / NHLBI NIH HHS / United States
R01 HG003054 / HG / NHGRI NIH HHS / United States
P41 RR003655 / RR / NCRR NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
R01 HL046380 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
N01HC45205 / HL / NHLBI NIH HHS / United States
HL007567-29 / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
HL086718 / HL / NHLBI NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
R01 GM073059 / GM / NIGMS NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
RR03655 / RR / NCRR NIH HHS / United States
N01HC95170 / HL / NHLBI NIH HHS / United States
N01HC95095 / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
N01 HC045134 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
N01HC48050 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC05187 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
R01 HL086718 / HL / NHLBI NIH HHS / United States
N01HC48047 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC95171 / HL / NHLBI NIH HHS / United States
N01HC45204 / HL / NHLBI NIH HHS / United States
T32 HL007567 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
R01 HL055673 / HL / NHLBI NIH HHS / United States
N01HC48048 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
N01HC95172 / HL / NHLBI NIH HHS / United States