title: Estrogen receptor gene variants are associated with anxiety disorders in older women.
abstract: BACKGROUND
  Estrogen is thought to play a key role in anxiety, but it remains unknown whether genetic variants in the estrogen receptors (ERs) can influence the risk of anxiety. This study investigated whether ESR1 and ESR2 gene variants were associated with specific anxiety disorders in postmenopausal women and evaluated the potential modifying effect of hormone treatment (HT) on these associations.
  
  
  METHODS
  One thousand and ninety-two community-dwelling women aged 65 years and older were recruited as part of the ESPRIT Study in Montpellier, France. Anxiety was assessed using the Mini-International Neuropsychiatry Interview (MINI), according to DSM-IV criteria. Two ESR1 and three ESR2 polymorphisms were genotyped.
  
  
  RESULTS
  The most common anxiety disorders were phobia (14.2%) and generalised anxiety disorder (GAD, 8%). The A allele of ESR2 rs1256049 was associated with an increased risk of GAD [OR: 2.06, 95% CI: 1.09-3.87], while both ESR1 polymorphisms were specifically associated with phobia. The C allele of ESR1 rs2234693 decreased the risk of phobia by 42% [95% CI: 0.41-0.83], and this remained significant even after Bonferroni correction. The G allele of ESR1 rs9340799 was associated with a 31% decreased phobia risk [95% CI: 0.49-0.96]. There was also evidence of a significant gene-environment interaction, where only women who were currently using HT had a reduced risk of phobia with these ESR1 gene variants.
  
  
  CONCLUSIONS
  This study confirms earlier findings of an association between ESR1 and global anxiety in older women, however these associations varied depending on the anxiety syndrome and the use of HT. The results also suggest that the ESR2 may contribute to the genetic vulnerability to GAD, but these findings require further confirmation.
authors.affiliation: Inserm, U1061, Nervous System Pathologies: Epidemiological and Clinical Research, Hôpital La Colombière, Montpellier, France. joanne.ryan@inserm.fr
authors.forename: Joanne
authors.initials: J
authors.lastname: Ryan
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Scali
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carrière
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Scarabin
authors.forename: Karen
authors.initials: K
authors.lastname: Ritchie
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Ancelin
mesh_terms: D000367:Age Factors; D000368:Aged; D001008:Anxiety Disorders / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D010698:Phobic Disorders / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012111:Residence Characteristics
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta