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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
- Source :
- PloS one, vol 15, iss 11, PLoS ONE, PLoS One (print), 15(11 November):e0230035. Public Library of Science, PLoS ONE, Vol 15, Iss 11, p e0230035 (2020)
- Publication Year :
- 2020
-
Abstract
- 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) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event. 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.
- Subjects :
- 0301 basic medicine
Oncology
Aging
Myocardial Infarction
Social Sciences
Genome-wide association study
Coronary Artery Disease
Disease
Cardiovascular Medicine
030204 cardiovascular system & hematology
Cardiovascular
Vascular Medicine
Coronary artery disease
Medical Conditions
0302 clinical medicine
Sociology
Consortia
Epidemiology
Medicine and Health Sciences
Coronary Heart Disease
2.1 Biological and endogenous factors
Prospective Studies
Myocardial infarction
Aetiology
Prospective cohort study
0303 health sciences
Multidisciplinary
Genomics
Single Nucleotide
3. Good health
Europe
Heart Disease
Cardiovascular Diseases
Cohort
Medicine
Research Article
medicine.medical_specialty
General Science & Technology
Science
Cardiology
Locus (genetics)
Polymorphism, Single Nucleotide
White People
03 medical and health sciences
Clinical Research
Internal medicine
Genome-Wide Association Studies
Genetics
medicine
Humans
Polymorphism
Alleles
Heart Disease - Coronary Heart Disease
030304 developmental biology
Genetic association
Whites
business.industry
Human Genome
Biology and Life Sciences
Computational Biology
Human Genetics
Cardiovascular Disease Risk
Genome Analysis
medicine.disease
Minor allele frequency
030104 developmental biology
Cross-Sectional Studies
Good Health and Well Being
Genetic Loci
business
Genome-Wide Association Study
2.4 Surveillance and distribution
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 15
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PLoS One (print)
- Accession number :
- edsair.doi.dedup.....f08ba115b3ce8f5520bc98edc09de30e