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.

<h4>Background</h4>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...

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Autores principales:	Julie Hahn, Yi-Ping Fu, Michael R Brown, Joshua C Bis, Paul S de Vries, Mary F Feitosa, Lisa R Yanek, Stefan Weiss, Franco Giulianini, Albert Vernon Smith, Xiuqing Guo, Traci M Bartz, Diane M Becker, Lewis C Becker, Eric Boerwinkle, Jennifer A Brody, Yii-Der Ida Chen, Oscar H Franco, Megan Grove, Tamara B Harris, Albert Hofman, Shih-Jen Hwang, Brian G Kral, Lenore J Launer, Marcello R P Markus, Kenneth M Rice, Stephen S Rich, Paul M Ridker, Fernando Rivadeneira, Jerome I Rotter, Nona Sotoodehnia, Kent D Taylor, André G Uitterlinden, Uwe Völker, Henry Völzke, Jie Yao, Daniel I Chasman, Marcus Dörr, Vilmundur Gudnason, Rasika A Mathias, Wendy Post, Bruce M Psaty, Abbas Dehghan, Christopher J O'Donnell, Alanna C Morrison
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9d94d892f87c4153a189fd83c7b58f38
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spelling	oai:doaj.org-article:9d94d892f87c4153a189fd83c7b58f382021-12-02T20:05:45ZGenetic 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.1932-620310.1371/journal.pone.0230035https://doaj.org/article/9d94d892f87c4153a189fd83c7b58f382020-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0230035https://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.Julie HahnYi-Ping FuMichael R BrownJoshua C BisPaul S de VriesMary F FeitosaLisa R YanekStefan WeissFranco GiulianiniAlbert Vernon SmithXiuqing GuoTraci M BartzDiane M BeckerLewis C BeckerEric BoerwinkleJennifer A BrodyYii-Der Ida ChenOscar H FrancoMegan GroveTamara B HarrisAlbert HofmanShih-Jen HwangBrian G KralLenore J LaunerMarcello R P MarkusKenneth M RiceStephen S RichPaul M RidkerFernando RivadeneiraJerome I RotterNona SotoodehniaKent D TaylorAndré G UitterlindenUwe VölkerHenry VölzkeJie YaoDaniel I ChasmanMarcus DörrVilmundur GudnasonRasika A MathiasWendy PostBruce M PsatyAbbas DehghanChristopher J O'DonnellAlanna C MorrisonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 15, Iss 11, p e0230035 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julie Hahn Yi-Ping Fu Michael R Brown Joshua C Bis Paul S de Vries Mary F Feitosa Lisa R Yanek Stefan Weiss Franco Giulianini Albert Vernon Smith Xiuqing Guo Traci M Bartz Diane M Becker Lewis C Becker Eric Boerwinkle Jennifer A Brody Yii-Der Ida Chen Oscar H Franco Megan Grove Tamara B Harris Albert Hofman Shih-Jen Hwang Brian G Kral Lenore J Launer Marcello R P Markus Kenneth M Rice Stephen S Rich Paul M Ridker Fernando Rivadeneira Jerome I Rotter Nona Sotoodehnia Kent D Taylor André G Uitterlinden Uwe Völker Henry Völzke Jie Yao Daniel I Chasman Marcus Dörr Vilmundur Gudnason Rasika A Mathias Wendy Post Bruce M Psaty Abbas Dehghan Christopher J O'Donnell Alanna C Morrison 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.
description	<h4>Background</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.
format	article
author	Julie Hahn Yi-Ping Fu Michael R Brown Joshua C Bis Paul S de Vries Mary F Feitosa Lisa R Yanek Stefan Weiss Franco Giulianini Albert Vernon Smith Xiuqing Guo Traci M Bartz Diane M Becker Lewis C Becker Eric Boerwinkle Jennifer A Brody Yii-Der Ida Chen Oscar H Franco Megan Grove Tamara B Harris Albert Hofman Shih-Jen Hwang Brian G Kral Lenore J Launer Marcello R P Markus Kenneth M Rice Stephen S Rich Paul M Ridker Fernando Rivadeneira Jerome I Rotter Nona Sotoodehnia Kent D Taylor André G Uitterlinden Uwe Völker Henry Völzke Jie Yao Daniel I Chasman Marcus Dörr Vilmundur Gudnason Rasika A Mathias Wendy Post Bruce M Psaty Abbas Dehghan Christopher J O'Donnell Alanna C Morrison
author_facet	Julie Hahn Yi-Ping Fu Michael R Brown Joshua C Bis Paul S de Vries Mary F Feitosa Lisa R Yanek Stefan Weiss Franco Giulianini Albert Vernon Smith Xiuqing Guo Traci M Bartz Diane M Becker Lewis C Becker Eric Boerwinkle Jennifer A Brody Yii-Der Ida Chen Oscar H Franco Megan Grove Tamara B Harris Albert Hofman Shih-Jen Hwang Brian G Kral Lenore J Launer Marcello R P Markus Kenneth M Rice Stephen S Rich Paul M Ridker Fernando Rivadeneira Jerome I Rotter Nona Sotoodehnia Kent D Taylor André G Uitterlinden Uwe Völker Henry Völzke Jie Yao Daniel I Chasman Marcus Dörr Vilmundur Gudnason Rasika A Mathias Wendy Post Bruce M Psaty Abbas Dehghan Christopher J O'Donnell Alanna C Morrison
author_sort	Julie Hahn
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.
title_short	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.
title_full	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.
title_fullStr	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.
title_full_unstemmed	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.
title_sort	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.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/9d94d892f87c4153a189fd83c7b58f38
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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.

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