» Articles » PMID: 25552592

Variants for HDL-C, LDL-C, and Triglycerides Identified from Admixture Mapping and Fine-mapping Analysis in African American Families

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.

Citing Articles

Genetic heterogeneity in cardiovascular disease across ancestries: Insights for mechanisms and therapeutic intervention.

Soremekun O, Dib M, Rajasundaram S, Fatumo S, Gill D Camb Prism Precis Med. 2024; 1:e8.

PMID: 38550935 PMC: 10953756. DOI: 10.1017/pcm.2022.13.


Obesity Pillars Roundtable: Body mass index and body composition in Black and Female individuals. Race-relevant or racist? Sex-relevant or sexist?.

Bays H, Gonsahn-Bollie S, Younglove C, Wharton S Obes Pillars. 2023; 4:100044.

PMID: 37990673 PMC: 10662008. DOI: 10.1016/j.obpill.2022.100044.


Strategies for the Genomic Analysis of Admixed Populations.

Tan T, Atkinson E Annu Rev Biomed Data Sci. 2023; 6:105-127.

PMID: 37127050 PMC: 10871708. DOI: 10.1146/annurev-biodatasci-020722-014310.


Genetic European Ancestry and Incident Diabetes in Black Individuals: Insights From the SPRINT Trial.

Parcha V, Heindl B, Kalra R, Bress A, Rao S, Pandey A Circ Genom Precis Med. 2022; 15(1):e003468.

PMID: 35089798 PMC: 8847245. DOI: 10.1161/CIRCGEN.121.003468.


Tractor uses local ancestry to enable the inclusion of admixed individuals in GWAS and to boost power.

Atkinson E, Maihofer A, Kanai M, Martin A, Karczewski K, Santoro M Nat Genet. 2021; 53(2):195-204.

PMID: 33462486 PMC: 7867648. DOI: 10.1038/s41588-020-00766-y.


References
1.
Basu A, Tang H, Lewis C, North K, Curb J, Quertermous T . Admixture mapping of quantitative trait loci for blood lipids in African-Americans. Hum Mol Genet. 2009; 18(11):2091-8. PMC: 2722229. DOI: 10.1093/hmg/ddp122. View

2.
Teslovich T, Musunuru K, Smith A, Edmondson A, Stylianou I, Koseki M . Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010; 466(7307):707-13. PMC: 3039276. DOI: 10.1038/nature09270. View

3.
Basu A, Tang H, Arnett D, Gu C, Mosley T, Kardia S . Admixture mapping of quantitative trait loci for BMI in African Americans: evidence for loci on chromosomes 3q, 5q, and 15q. Obesity (Silver Spring). 2009; 17(6):1226-31. PMC: 2929755. DOI: 10.1038/oby.2009.24. View

4.
Wang H, Eckel R . Lipoprotein lipase: from gene to obesity. Am J Physiol Endocrinol Metab. 2009; 297(2):E271-88. DOI: 10.1152/ajpendo.90920.2008. View

5.
Heid I, Boes E, Muller M, Kollerits B, Lamina C, Coassin S . Genome-wide association analysis of high-density lipoprotein cholesterol in the population-based KORA study sheds new light on intergenic regions. Circ Cardiovasc Genet. 2009; 1(1):10-20. DOI: 10.1161/CIRCGENETICS.108.776708. View