title: The role of allelic variation in estrogen receptor genes and major depression in the Nurses Health Study.
abstract: OBJECTIVE
  The role of exogenous and endogenous sex hormones in the etiology of depression remains elusive, in part because sex hormone variation is often correlated with behaviors, life stage changes, and other factors that may influence depression. Estrogen receptor alpha (ESR1) and beta (ESR2) are known to regulate gene expression and estrogen response in areas of the brain associated with major depression and are unlikely to be correlated with exogenous factors that may influence depression.
  
  
  METHODS
  We examined whether functional polymorphisms in these genes are associated with lifetime major depression and chronic major depression among a sample of women from the Nurses' Health Study II (N = 2527). DSM-IV depressive disorder symptoms were assessed by structured interview in 2007. Genotyping was performed on DNA extracted from blood using Taq-man.
  
  
  RESULTS
  Women with the AA alleles of ESR2 RS4986938 had the higher prevalence of lifetime major depression than women with other allele frequencies (36.7 % for those with AA versus 28.5 % with GA and 29.1 % with GG, p = 0.02) and chronic major depression (14.7 % for those with AA versus 9.3 % with GA and 9.1 % with GG, p = 0.01). History of post-menopausal hormone (PMH) use modified the association of ESR1 polymorphism RS2234693 with any lifetime depression; specifically, those with the TT allele had the highest risk of lifetime depression among PMH users, and the lowest risk of depression among non-PMH users (p value for interaction = 0.02). Further, carriers of the AA alleles in ESR1 polymorphism RS9340799 had increased prevalence of lifetime major depression only among lifetime PMH users (p = 0.007).
  
  
  CONCLUSIONS
  Our findings support the hypothesis that estrogen receptor polymorphisms influence risk for major depression; the role of estrogen receptors and other sex steroid-related genetic factors may provide unique insights into etiology.
authors.affiliation: Department of Epidemiology, Columbia University, Mailman School of Public Health, 722 West 168th Street, New York, NY, 10032, USA. kmk2104@columbia.edu.
authors.forename: K
authors.initials: K
authors.lastname: Keyes
authors.affiliation: Department of Epidemiology, Harvard University, 181 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: J
authors.initials: J
authors.lastname: Agnew-Blais
authors.affiliation: Department of Social and Behavioral Sciences, Harvard University, 677 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Roberts
authors.affiliation: Department of Epidemiology, Columbia University, Mailman School of Public Health, 722 West 168th Street, New York, NY, 10032, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hamilton
authors.affiliation: Department of Epidemiology, Harvard University, 181 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: I
authors.initials: I
authors.lastname: De Vivo
authors.affiliation: Harvard T.H. Chan School of Public Health, Harvard University, 655 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ranu
authors.affiliation: Department of Epidemiology, Columbia University, Mailman School of Public Health, 722 West 168th Street, New York, NY, 10032, USA.
authors.forename: K
authors.initials: K
authors.lastname: Koenen
mesh_terms: D000328:Adult; D000483:Alleles; D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009726:Nurses / Q000523:psychology* / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta
keywords: Depression; Estrogen; Estrogen receptor alpha; Estrogen receptor beta; Hormones; Nurses; Post-menopausal hormone use