Genomewide Association Analysis of Coronary Artery Disease

By N. Samani, J. Erdmann, A. Hall, C. Hengstenberg, M. Mangino, Bjoern Mayer, R. Dixon, T. Meitinger, P. Braund, H. Wichmann and 24 more. New England Journal of Medicine, 2007

2,121 citations recorded by the source corpus.

BACKGROUND Modern genotyping platforms permit a systematic search for inherited components of complex diseases. We performed a joint analysis of two genomewide association studies of coronary artery disease. METHODS We first identified chromosomal loci that were strongly associated with coronary artery disease in the Wellcome Trust Case Control Consortium (WTCCC) study (which involved 1926 case subjects with coronary artery disease and 2938 controls) and looked for replication in the German MI [Myocardial Infarction] Family Study (which involved 875 case subjects with myocardial infarction and 1644 controls). Data on other single-nucleotide polymorphisms (SNPs) that were significantly associated with coronary artery disease in either study (P<0.001) were then combined to identify additional loci with a high probability of true association. Genotyping in both studies was performed with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). RESULTS Of thousands of chromosomal loci studied, the same locus had the strongest association with coronary artery disease in both the WTCCC and the German studies: chromosome 9p21.3 (SNP, rs1333049) (P=1.80×10−14 and P=3.40×10−6, respectively). Overall, the WTCCC study revealed nine loci that were strongly associated with coronary artery disease (P<1.2×10−5 and less than a 50% chance of being falsely positive). In addition to chromosome 9p21.3, two of these loci were successfully replicated (adjusted P<0.05) in the German study: chromosome 6q25.1 (rs6922269) and chromosome 2q36.3 (rs2943634). The combined analysis of the two studies identified four additional loci significantly associated with coronary artery disease (P<1.3×10−6) and a high probability (>80%) of a true association: chromosomes 1p13.3 (rs599839), 1q41 (rs17465637), 10q11.21 (rs501120), and 15q22.33 (rs17228212). CONCLUSIONS We identified several genetic loci that, individually and in aggregate, substantially affect the risk of development of coronary artery disease.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/be65a4542d456eec462173ef6a2494cd227ddc31

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Citations in the corpus

Linking disease associations with regulatory information in the human genome (2012, methodology): “This is consistent with results from fine-mapping analyses that indicate that multiple variants in the linkage disequilibrium region surrounding a lead SNP appear to play a role in the phenotype of interest (Chung et al. 2011; Sanna et al. 2011).”
Genetics Meets Metabolomics: A Genome-Wide Association Study of Metabolite Profiles in Human Serum (2008, background): “Recent genome-wide association (GWA) studies have identified a number of genetic polymorphisms that convey an increased risk for developing diabetes, coronary artery disease, rheumatoid arthritis, and other common diseases [1–4].”
From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus (2010, neutral): “The full Methods provides information about all experimental procedures: (1) description of association analyses in the population cohorts; (2) description of genotype-expression analyses in human liver, subcutaneous adipose, and omental adipose samples; (3) details for generation of luciferase expr”
A review on coronary artery disease, its risk factors, and therapeutics (2019, background): “In such studies, it was reported that 396 single‐nucleotide polymorphisms (SNPs) were associated with CAD, of which 30 SNPs were clustered in nine chromosomal regions (Samani et al., 2007).”
Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database. (2010, background): “36 Interest-ingly, replicated genetic loci identiﬁed in psoriasis such as CDKALI have been shown to be associated with Type 2 diabetes.”
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis (2010, background): “This analysis takes the number of independent loci showing genome-wide significant associations with T2D beyond 35.”
Meta-analysis methods for genome-wide association studies and beyond (2013, methodology): “Specifically, the Wellcome Trust Case Control Consortium has used the Bayes factor 38 , whereas the Coronary Artery Disease Consortium has presented results as posterior probabilities that a variant is null 39 .”