Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5

Nolan, Daniel K, Sutton, Beth, Haynes, Carol, Johnson, Jessica, Sebek, Jacqueline, Dowdy, Elaine, Crosslin, David, Crossman, David, Sketch, Michael H, Granger, Christopher B, Seo, David, Goldschmidt-Clermont, Pascal, Kraus, William E, Gregory, Simon G, Hauser, Elizabeth R and Shah, Svati H (2012) Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5. Genetics, 13. p. 12. ISSN 1943-2631

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Abstract

Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas).

Item Type:	Article
Uncontrolled Keywords:	atherosclerosis,cholesterol, ldl,chromosome mapping,chromosomes, human, pair 5,coronary artery disease,genetic association studies,genetic linkage,humans,linkage disequilibrium,lipids,polymorphism, single nucleotide,quantitative trait, heritable,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit
Depositing User:	Pure Connector
Date Deposited:	20 Jan 2014 16:02
Last Modified:	24 Oct 2022 05:34
URI:	https://ueaeprints.uea.ac.uk/id/eprint/46183
DOI:	10.1186/1471-2156-13-12

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