|Title||Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Hahn, J, Fu, Y-P, Brown, MR, Bis, JC, de Vries, PS, Feitosa, MF, Yanek, LR, Weiss, S, Giulianini, F, Smith, AVernon, Guo, X, Bartz, TM, Becker, DM, Becker, LC, Boerwinkle, E, Brody, JA, Chen, Y-DIda, Franco, OH, Grove, M, Harris, TB, Hofman, A, Hwang, S-J, Kral, BG, Launer, LJ, Markus, MRP, Rice, KM, Rich, SS, Ridker, PM, Rivadeneira, F, Rotter, JI, Sotoodehnia, N, Taylor, KD, Uitterlinden, AG, Völker, U, Völzke, H, Yao, J, Chasman, DI, Dörr, M, Gudnason, V, Mathias, RA, Post, W, Psaty, BM, Dehghan, A, O'Donnell, CJ, Morrison, AC|
BACKGROUND: Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome.
METHODS AND RESULTS: Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF)
CONCLUSION: This study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.
|Alternate Journal||PLoS One|
|PubMed Central ID||PMC7665790|