A genome-wide linkage scan identifies multiple quantitative trait loci for HDL-cholesterol levels in families with premature CAD and MI
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-06-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520410181 |
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doaj-48a701ef30c84160a9ea692485c2ada9 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Rong Yang Lin Li Sara Bretschger Seidelmann Gong-Qing Shen Sonia Sharma Shaoqi Rao Kalil G. Abdullah Kenneth G. MacKinlay Robert C. Elston Qiuyun Chen Eric J. Topol Qing Kenneth Wang |
| spellingShingle |
Rong Yang Lin Li Sara Bretschger Seidelmann Gong-Qing Shen Sonia Sharma Shaoqi Rao Kalil G. Abdullah Kenneth G. MacKinlay Robert C. Elston Qiuyun Chen Eric J. Topol Qing Kenneth Wang A genome-wide linkage scan identifies multiple quantitative trait loci for HDL-cholesterol levels in families with premature CAD and MI Journal of Lipid Research genetics linkage single nucleotide polymorphism high density lipoprotein cholesterol coronary artery disease myocardial infarction |
| author_facet |
Rong Yang Lin Li Sara Bretschger Seidelmann Gong-Qing Shen Sonia Sharma Shaoqi Rao Kalil G. Abdullah Kenneth G. MacKinlay Robert C. Elston Qiuyun Chen Eric J. Topol Qing Kenneth Wang |
| author_sort |
Rong Yang |
| title |
A genome-wide linkage scan identifies multiple quantitative trait loci for HDL-cholesterol levels in families with premature CAD and MI |
| title_short |
A genome-wide linkage scan identifies multiple quantitative trait loci for HDL-cholesterol levels in families with premature CAD and MI |
| title_full |
A genome-wide linkage scan identifies multiple quantitative trait loci for HDL-cholesterol levels in families with premature CAD and MI |
| title_fullStr |
A genome-wide linkage scan identifies multiple quantitative trait loci for HDL-cholesterol levels in families with premature CAD and MI |
| title_full_unstemmed |
A genome-wide linkage scan identifies multiple quantitative trait loci for HDL-cholesterol levels in families with premature CAD and MI |
| title_sort |
genome-wide linkage scan identifies multiple quantitative trait loci for hdl-cholesterol levels in families with premature cad and mi |
| publisher |
Elsevier |
| series |
Journal of Lipid Research |
| issn |
0022-2275 |
| publishDate |
2010-06-01 |
| description |
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 × 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. |
| topic |
genetics linkage single nucleotide polymorphism high density lipoprotein cholesterol coronary artery disease myocardial infarction |
| url |
http://www.sciencedirect.com/science/article/pii/S0022227520410181 |
| work_keys_str_mv |
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| _version_ |
1721504334405959680 |
| spelling |
doaj-48a701ef30c84160a9ea692485c2ada92021-04-28T06:04:11ZengElsevierJournal of Lipid Research0022-22752010-06-0151614421451A genome-wide linkage scan identifies multiple quantitative trait loci for HDL-cholesterol levels in families with premature CAD and MIRong Yang0Lin Li1Sara Bretschger Seidelmann2Gong-Qing Shen3Sonia Sharma4Shaoqi Rao5Kalil G. Abdullah6Kenneth G. MacKinlay7Robert C. Elston8Qiuyun Chen9Eric J. Topol10Qing Kenneth Wang11Center for Cardiovascular Genetics, Department of Molecular Cardiology Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, ChinaCenter for Cardiovascular Genetics, Department of Molecular Cardiology Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106Center for Cardiovascular Genetics, Department of Molecular Cardiology Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106Center for Cardiovascular Genetics, Department of Molecular Cardiology Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106Center for Cardiovascular Genetics, Department of Molecular Cardiology Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106Center for Cardiovascular Genetics, Department of Molecular Cardiology Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106Center for Cardiovascular Genetics, Department of Molecular Cardiology Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106Center for Cardiovascular Genetics, Department of Molecular Cardiology Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106Center for Cardiovascular Genetics, Department of Molecular Cardiology Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106Scripps Genomic Medicine, The Scripps Research Institute, La Jolla, CA 92037Center for Cardiovascular Genetics, Department of Molecular Cardiology Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, ChinaPlasma 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 × 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.http://www.sciencedirect.com/science/article/pii/S0022227520410181geneticslinkagesingle nucleotide polymorphismhigh density lipoprotein cholesterolcoronary artery diseasemyocardial infarction |