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Post-Genomic Update...
Post-Genomic Update on a Classical Candidate Gene for Coronary Artery Disease: ESR1
- Article/chapterEnglish2011
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LIBRIS-ID:oai:lup.lub.lu.se:a1baa9e1-ee38-42e0-a40f-491f2708f48d
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https://lup.lub.lu.se/record/2333117URI
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https://doi.org/10.1161/CIRCGENETICS.111.960583DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
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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 alpha (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 = approximate to 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 = approximate to 6000), WTCCC (N = approximate to 7400), and Framingham (N = approximate to 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 ER alpha 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. (Circ Cardiovasc Genet. 2011;4:647-654.)
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Lluis-Ganella, Carla
(author)
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Subirana, Isaac
(author)
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Senti, Mariano
(author)
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Willenborg, Christina
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Musameh, Muntaser D.
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Schwartz, Stephen M.
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O'Donnell, Christopher J.
(author)
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Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome
(author)
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Salomaa, Veikko
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Elosua, Roberto
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Kardiovaskulär forskning - hypertoniForskargrupper vid Lunds universitet
(creator_code:org_t)
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In:Circulation: Cardiovascular Genetics4:6, s. 357-6471942-325X
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Lucas, Gavin
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Lluis-Ganella, C ...
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Subirana, Isaac
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Senti, Mariano
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Willenborg, Chri ...
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Musameh, Muntase ...
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Schwartz, Stephe ...
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O'Donnell, Chris ...
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Melander, Olle
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Salomaa, Veikko
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Elosua, Roberto
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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Circulation: Car ...
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Lund University