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Olle Melander

Principal investigator

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Post-Genomic Update on a Classical Candidate Gene for Coronary Artery Disease: ESR1


  • Gavin Lucas
  • Carla Lluis-Ganella
  • Isaac Subirana
  • Mariano Senti
  • Christina Willenborg
  • Muntaser D. Musameh
  • Stephen M. Schwartz
  • Christopher J. O'Donnell
  • Olle Melander
  • Veikko Salomaa
  • Roberto Elosua

Summary, in English

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.)


  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year







Circulation: Cardiovascular Genetics





Document type

Journal article


American Heart Association


  • Cardiac and Cardiovascular Systems


  • coronary artery disease
  • estrogen receptor alpha
  • menopause
  • polymorphism
  • single nucleotide
  • genetic association studies
  • meta-analysis



Research group

  • Cardiovascular Research - Hypertension


  • ISSN: 1942-325X