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Admixture mapping of quantitative trait loci for blood lipids in African-Americans.

作者信息

Basu Analabha, Tang Hua, Lewis Cora E, North Kari, Curb J David, Quertermous Thomas, Mosley Thomas H, Boerwinkle Eric, Zhu Xiaofeng, Risch Neil J

机构信息

Institute for Human Genetics, University of California San Francisco, 513 Parnassus Avenue, Room 901F HSW, San Francisco, CA 94143, USA.

出版信息

Hum Mol Genet. 2009 Jun 1;18(11):2091-8. doi: 10.1093/hmg/ddp122. Epub 2009 Mar 20.


DOI:10.1093/hmg/ddp122
PMID:19304782
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2722229/
Abstract

Blood lipid levels, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), are highly heritable traits and major risk factors for atherosclerotic cardiovascular disease (CVD). Using individual ancestry estimates at marker locations across the genome, we present a novel quantitative admixture mapping analysis of all three lipid traits in a large sample of African-Americans from the Family Blood Pressure Program. Regression analysis was performed with both total and marker-location-specific European ancestry as explanatory variables, along with demographic covariates. Robust permutation analysis was used to assess statistical significance. Overall European ancestry was significantly correlated with HDL-C (negatively) and TG (positively), but not with LDL-C. We found strong evidence for a novel locus underlying HDL-C on chromosome 8q, which correlated negatively with European ancestry (P = .0014); the same location also showed positive correlation of European ancestry with TG levels. A region on chromosome 14q also showed significant negative correlation between HDL-C levels and European ancestry. On chromosome 15q, a suggestive negative correlation of European ancestry with TG and positive correlation with HDL-C was observed. Results with LDL-C were less significant overall. We also found significant evidence for genome-wide ancestry effects underlying the joint distribution of HDL-C and TG, not fully explained by the locus on chromosome 8. Our results are consistent with a genetic contribution to and may explain the healthier HDL-C and TG profiles found in Blacks versus Whites. The identified regions provide locations for follow-up studies of genetic variants underlying lipid variation in African-Americans and possibly other populations.

摘要

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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Admixture mapping of quantitative trait loci for BMI in African Americans: evidence for loci on chromosomes 3q, 5q, and 15q.

Obesity (Silver Spring). 2009-6

[2]
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.

Nat Genet. 2008-2

[3]
Newly identified loci that influence lipid concentrations and risk of coronary artery disease.

Nat Genet. 2008-2

[4]
A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study.

BMC Med Genet. 2007-9-19

[5]
Cholesterol fractions and apolipoproteins as risk factors for heart disease mortality in older men.

Arch Intern Med. 2007-7-9

[6]
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.

Science. 2007-6-1

[7]
Common ABCA1 variants, HDL levels, and cellular cholesterol efflux in subjects with familial low HDL.

J Lipid Res. 2007-6

[8]
Quantitative trait locus on 15q for a metabolic syndrome variable derived from factor analysis.

Obesity (Silver Spring). 2007-3

[9]
Genetic ancestry, population sub-structure, and cardiovascular disease-related traits among African-American participants in the CARDIA Study.

Hum Genet. 2007-6

[10]
Genetic epistasis in the VLDL catabolic pathway is associated with deleterious variations on triglyceridemia in obese subjects.

Int J Obes (Lond). 2007-8

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