Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

2.50
Hdl Handle:
http://hdl.handle.net/11287/620321
Title:
Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function
Authors:
Wild, P. S. [et al]; Sharp, Andrew
Abstract:
BACKGROUND. Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS. A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS. The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION. The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.
Citation:
Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function. 2017 Apr 10. Journal of Clinical Investigation.
Publisher:
American Society for Clinical Investigation
Journal:
Journal of Clinical Investigation
Issue Date:
10-Apr-2017
URI:
http://hdl.handle.net/11287/620321
DOI:
10.1172/JCI84840
Additional Links:
https://doi.org/10.1172/JCI84840
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
Appears in Collections:
Cardiology; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorWild, P. S. [et al]en
dc.contributor.authorSharp, Andrewen
dc.date.accessioned2017-04-19T11:07:11Z-
dc.date.available2017-04-19T11:07:11Z-
dc.date.issued2017-04-10-
dc.identifier.citationLarge-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function. 2017 Apr 10. Journal of Clinical Investigation.en
dc.identifier.doi10.1172/JCI84840-
dc.identifier.urihttp://hdl.handle.net/11287/620321-
dc.description.abstractBACKGROUND. Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS. A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS. The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION. The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.en
dc.language.isoenen
dc.publisherAmerican Society for Clinical Investigationen
dc.relation.urlhttps://doi.org/10.1172/JCI84840en
dc.subjectWessex Classification Subject Headings::Cardiologyen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleLarge-scale genome-wide analysis identifies genetic variants associated with cardiac structure and functionen
dc.typeJournal Articleen
dc.identifier.journalJournal of Clinical Investigationen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionPublisheden
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