Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease

We identify the SLC22A3-LPAL2-LPA gene cluster as a strong susceptibility locus for coronary artery disease (CAD) through a genome-wide haplotype association (GWHA) study. This locus was not identified from previous genome-wide association (GWA) studies focused on univariate analyses of SNPs. The proposed approach may have wide utility for analyzing GWA data for other complex traits.

[1]  A. Evans,et al.  A case-control study of lipoprotein particles in two populations at contrasting risk for coronary heart disease. The ECTIM Study. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[2]  E. Boerwinkle,et al.  Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. , 1992, The Journal of clinical investigation.

[3]  J. Ordovás,et al.  Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid Research Clinics Coronary Primary Prevention Trial. , 1994, JAMA.

[4]  D. Arveiler,et al.  Sequence polymorphisms in the apolipoprotein(a) gene and their association with lipoprotein(a) levels and myocardial infarction. The ECTIM Study. , 1999, Atherosclerosis.

[5]  C. Hengstenberg,et al.  Association of Polymorphisms of the Apolipoprotein(a) Gene With Lipoprotein(a) Levels and Myocardial Infarction , 2003, Circulation.

[6]  C. Gieger,et al.  KORA-gen - Resource for Population Genetics, Controls and a Broad Spectrum of Disease Phenotypes , 2005 .

[7]  J. Erdmann,et al.  Distinct Heritable Patterns of Angiographic Coronary Artery Disease in Families With Myocardial Infarction , 2005, Circulation.

[8]  Fabrizio Gagliardi,et al.  Building an infrastructure for scientific Grid computing: status and goals of the EGEE project , 2005, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[9]  Michael Krawczak,et al.  PopGen: Population-Based Recruitment of Patients and Controls for the Analysis of Complex Genotype-Phenotype Relationships , 2006, Public Health Genomics.

[10]  C. Gieger,et al.  Genomewide association analysis of coronary artery disease. , 2007, The New England journal of medicine.

[11]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[12]  K. Mossman.  The Wellcome Trust Case Control Consortium, U.K. , 2008 .

[13]  B. Browning,et al.  Haplotypic analysis of Wellcome Trust Case Control Consortium data , 2008, Human Genetics.