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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.

Monday,2021-01-25 16:24 America/Los_Angeles — ecterry
TitleGenetic 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 TypeJournal Article
Year of Publication2020
AuthorsHahn, 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-DI, 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
JournalPLoS One
Volume15
Issue11
Paginatione0230035
Date Published2020
ISSN1932-6203
KeywordsAging, Coronary Artery Disease, Cross-Sectional Studies, Europe, European Continental Ancestry Group, Genetic Loci, Genome-Wide Association Study, Humans, Myocardial Infarction, Polymorphism, Single Nucleotide, Prospective Studies
Abstract<p><b>BACKGROUND: </b>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.</p><p><b>METHODS AND RESULTS: </b>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.</p><p><b>CONCLUSION: </b>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.</p>
DOI10.1371/journal.pone.0230035
Alternate JournalPLoS One
PubMed ID33186364
PubMed Central IDPMC7665790
Grant ListR01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL141291 / HL / NHLBI NIH HHS / United States
N01 AG012100 / AG / NIA NIH HHS / United States
HHSN271201200022C / DA / NIDA NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
U01 HL072518 / HL / NHLBI NIH HHS / United States
M01 RR000052 / RR / NCRR NIH HHS / United States
HHSN268201100037C / HL / NHLBI NIH HHS / United States
HHSN268201500003I / HL / NHLBI NIH HHS / United States
N01 HC095159 / HC / NHLBI NIH HHS / United States
N01 HC095160 / HC / NHLBI NIH HHS / United States
N01 HC095161 / HC / NHLBI NIH HHS / United States
N01 HC095162 / HC / NHLBI NIH HHS / United States
N01 HC095163 / HC / NHLBI NIH HHS / United States
N01 HC095164 / HC / NHLBI NIH HHS / United States
N01 HC095165 / HC / NHLBI NIH HHS / United States
N01 HC095166 / HC / NHLBI NIH HHS / United States
N01 HC095167 / HC / NHLBI NIH HHS / United States
N01 HC095168 / HC / NHLBI NIH HHS / United States
N01 HC095169 / HC / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States
ePub date: 
20/11

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