Post-genomic update on a classical candidate gene for coronary artery disease: ESR1.

2.50
Hdl Handle:
http://hdl.handle.net/2336/227416
Title:
Post-genomic update on a classical candidate gene for coronary artery disease: ESR1.
Authors:
Lucas, Gavin; Lluís-Ganella, Carla; Subirana, Isaac; Sentí, Mariano; Willenborg, Christina; Musameh, Muntaser D; Schwartz, Stephen M; O'Donnell, Christopher J; Melander, Olle; Salomaa, Veikko; Elosua, Roberto; Thorgeirsson, Gudmundur
Citation:
Circ. Cardiovasc. Genet. 2011, 4(6):647-54
Issue Date:
Dec-2011
Abstract:
BACKGROUND: After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor α (ESR1) have shown conflicting results, although only a limited range of variation in the gene has been investigated. METHODS AND RESULTS: We exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question of ESR1's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N=≈87,000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions of ESR1. In addition to samples from the MIGen (N=≈6000), WTCCC (N=≈7400), and Framingham (N=≈3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ERα in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout the ESR1 gene in modifying risk of CAD, either in the general population or as a function of sex. CONCLUSIONS: We suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.
Additional Links:
http://dx.doi.org/10.1161/CIRCGENETICS.111.960583
Rights:
Archived with thanks to Circulation. Cardiovascular genetics

Full metadata record

DC FieldValue Language
dc.contributor.authorLucas, Gavinen_GB
dc.contributor.authorLluís-Ganella, Carlaen_GB
dc.contributor.authorSubirana, Isaacen_GB
dc.contributor.authorSentí, Marianoen_GB
dc.contributor.authorWillenborg, Christinaen_GB
dc.contributor.authorMusameh, Muntaser Den_GB
dc.contributor.authorSchwartz, Stephen Men_GB
dc.contributor.authorO'Donnell, Christopher Jen_GB
dc.contributor.authorMelander, Olleen_GB
dc.contributor.authorSalomaa, Veikkoen_GB
dc.contributor.authorElosua, Robertoen_GB
dc.contributor.authorThorgeirsson, Gudmunduren_GB
dc.date.accessioned2012-06-04T11:33:17Z-
dc.date.available2012-06-04T11:33:17Z-
dc.date.issued2011-12-
dc.date.submitted2012-06-04-
dc.identifier.citationCirc. Cardiovasc. Genet. 2011, 4(6):647-54en_GB
dc.identifier.issn1942-3268-
dc.identifier.pmid21984528-
dc.identifier.doi10.1161/CIRCGENETICS.111.960583-
dc.identifier.urihttp://hdl.handle.net/2336/227416-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractBACKGROUND: After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor α (ESR1) have shown conflicting results, although only a limited range of variation in the gene has been investigated. METHODS AND RESULTS: We exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question of ESR1's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N=≈87,000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions of ESR1. In addition to samples from the MIGen (N=≈6000), WTCCC (N=≈7400), and Framingham (N=≈3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ERα in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout the ESR1 gene in modifying risk of CAD, either in the general population or as a function of sex. CONCLUSIONS: We suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system.en_GB
dc.description.sponsorshipNational Institutes of Health R01 HL087676 Wellcome Trust 085475 National Heart, Lung, and Blood institute Boston University N01-HC-25195 European Regional Development Fund Spanish Ministry of Science and Innovation through the Carlos III Health Institute [CIBER Epidemiolog a y Salud Publica, Red HERACLES] RD06/0009 PI061254 PI09/90506 Catalan Research and Technology Innovation Interdepartmental Commission SGR 1195 Juan de la Cierva Program, Ministerio de Educacion JCI-2009-04684 ACC1O (RD08-1-0024)en_GB
dc.language.isoenen
dc.publisherLippincott Williams & Wilkinsen_GB
dc.relation.urlhttp://dx.doi.org/10.1161/CIRCGENETICS.111.960583en_GB
dc.rightsArchived with thanks to Circulation. Cardiovascular geneticsen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshCoronary Artery Diseaseen_GB
dc.subject.meshEstrogen Receptor alphaen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGenome-Wide Association Studyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshRisk Factorsen_GB
dc.titlePost-genomic update on a classical candidate gene for coronary artery disease: ESR1.en
dc.typeArticleen
dc.contributor.departmentCardiovascular Epidemiology and Genetics Group, Institut Municipal d'Investigació Mèdica, Barcelona, Spain. glucas@imim.esen_GB
dc.identifier.journalCirculation. Cardiovascular geneticsen_GB

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