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A genome-wide linkage scan identifies multiple quantitative trait loci for HDL-cholesterol levels in families with premature CAD and MI.
- Source :
-
Journal of lipid research [J Lipid Res] 2010 Jun; Vol. 51 (6), pp. 1442-51. Date of Electronic Publication: 2010 Jan 14. - Publication Year :
- 2010
-
Abstract
- Plasma HDL cholesterol levels (HDL-C) are an independent predictor of coronary artery disease (CAD). We have completed a genome-wide linkage scan for HDL-C in a US cohort consisting of 388 multiplex families with premature CAD (GeneQuest). The heritability of HDL-C in GeneQuest was 0.37 with gender and age as covariates (P = 5.1 x 10(-4)). Two major quantitative trait loci (QTL) for log-transformed HDL-C adjusted for age and gender were identified onto chromosomes 7p22 and 15q25 with maximum multipoint logarithm of odds (LOD) scores of 3.76 and 6.69, respectively. Fine mapping decreased the 7p22 LOD score to a nonsignificant level of 3.09 and split the 15q25 QTL into two loci, one minor QTL on 15q22 (LOD = 2.73) that spanned the LIPC gene, and the other at 15q25 (LOD = 5.63). A family-based quantitative transmission disequilibrium test (QTDT) revealed significant association between variant rs1800588 in LIPC and HDL-C in the GeneQuest population (P = 0.0067), which may account for the minor QTL on 15q22. The 15q25 QTL is the most significant locus identified for HDL-C to date, and these results provide a framework for the ultimate identification of the underlying HDL-C variant and gene on chromosomes 15q25, which will provide insights into novel regulatory mechanisms of HDL-C metabolism.
- Subjects :
- Age Factors
Cholesterol, HDL blood
Chromosomes, Human genetics
Cloning, Molecular
Female
Humans
Likelihood Functions
Linkage Disequilibrium
Male
Middle Aged
Sex Factors
Cholesterol, HDL genetics
Chromosome Mapping
Coronary Artery Disease genetics
Genome-Wide Association Study
Myocardial Infarction genetics
Quantitative Trait Loci genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1539-7262
- Volume :
- 51
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of lipid research
- Publication Type :
- Academic Journal
- Accession number :
- 20075193
- Full Text :
- https://doi.org/10.1194/jlr.M004325