title: Involvement of GPR50 polymorphisms in depression: independent replication in a prospective elderly cohort.
abstract: BACKGROUND
  Despite the explosion in genetic association studies over the last decade, clearly identified genetic risk factors for depression remain scarce and replication studies are becoming increasingly important. G-protein-coupled receptor 50 (GPR50) has been implicated in psychiatric disorders in a small number of studies, although not consistently.
  
  
  METHODS
  Data were obtained from 1010 elderly men and women from the prospective population-based ESPRIT study. Logistic regression and survival models were used to determine whether three common GPR50 polymorphisms were associated with depression prevalence or the incidence of depression over 12-years. The analyses were adjusted for a range of covariates such as comorbidity and cholesterol levels, to determine independent associations.
  
  
  RESULTS
  All three variants showed some evidence of an association with late-life depression in women, although these were not consistent across outcomes, the overall effect sizes were relatively small, and most would not remain significant after correction for multiple testing. Women heterozygous for rs13440581, had a 1.6-fold increased risk of baseline depression, while the odds of depression comorbid with anxiety were increased fourfold for women homozygous for the minor allele of rs2072621. When depressed women at baseline were excluded from the analysis, however, neither variant was associated with the 12-year incidence of depression. In contrast, rs561077 was associated with a 1.8-fold increased risk of incident depression specifically. No significant associations were observed in men.
  
  
  CONCLUSIONS
  Our results thus provide only weak support for the involvement of GPR50 variants in late-life depression, which appear specific to certain subgroups of depressed individuals (i.e., women and those with more severe forms of depression).
authors: Inserm, U1061 Montpellier, F-34093, France ; Univ Montpellier 1, U1061 Montpellier, France ; CDE, Murdoch Childrens Research Institute, Royal Children's Hospital Parkville, Victoria, 3052, Australia ; Department of Paediatrics, University of Melbourne Parkville, Victoria, 3052, Australia.
authors: Joanne
authors: J
authors: Ryan
authors: Inserm, U1061 Montpellier, F-34093, France ; Univ Montpellier 1, U1061 Montpellier, France.
authors: Isabelle
authors: I
authors: Carrière
authors: Inserm, U1061 Montpellier, F-34093, France ; Univ Montpellier 1, U1061 Montpellier, France ; Faculty of Medicine, Imperial College London, W12 0NN, U.K.
authors: Karen
authors: K
authors: Ritchie
authors: Inserm, U1061 Montpellier, F-34093, France ; Univ Montpellier 1, U1061 Montpellier, France.
authors: Marie-Laure
authors: ML
authors: Ancelin
mesh_terms: D017668:Age of Onset; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D015897:Comorbidity; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012737:Sex Factors
chemical_list: D000928:Antidepressive Agents; C509754:GPR50 protein, human; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled
keywords: Antidepressants; GPCR; GPR50; candidate gene; late-life depression; lipid levels