title: Obesity genes and risk of major depressive disorder in a multiethnic population: a cross-sectional study.
abstract: OBJECTIVE
  Observational studies have shown a positive association between obesity (body mass index [BMI] ≥ 30 kg/m2) and depression. Around 120 obesity-associated loci have been identified, but genetic variants associated with depression remain elusive. Recently, our team reported that the fat mass and obesity-associated (FTO) gene rs9939609 obesity-risk variant is paradoxically inversely associated with the risk of depression. This finding raises the question as to whether other obesity-associated genetic variants are also associated with depression.
  
  
  METHODS
  Twenty-one obesity gene variants other than FTO were selected from a custom ∼50,000 single-nucleotide polymorphisms (SNPs) genotyping array (ITMAT-Broad-CARe array). Associations of these 21 SNPs and an unweighted genotype score with BMI and major depressive disorder (determined using the DSM-IV diagnostic criteria) were tested in 3,209 cases and 14,195 noncases, using baseline data collected from July 2001 to August 2003 from the multiethnic EpiDREAM study.
  
  
  RESULTS
  Body mass index was positively associated with depression status (odds ratio [OR] = 1.02; 95% CI, 1.02-1.03 per BMI unit; P = 2.9 × 10(-12), adjusted for age, sex, and ethnicity). Six of 21 genetic variants (rs1514176 [TNN13K], rs2206734 [CDKAL1], rs11671664 [GIPR], rs2984618 [TAL1], rs3824755 [NT5C2], and rs7903146 [TCF7L2]) and the genotype score were significantly associated with BMI (1.47 × 10(-14) ≤ P ≤ .04). Of the 21 SNPs, TAL1 rs2984618 obesity-risk allele was associated with a higher risk of major depressive disorder (P = 1.79 × 10(-4), adjusted for age, sex, BMI, and ethnicity), and BDNF rs1401635 demonstrated significant ethnic-dependent association with major depressive disorder (OR = 0.88; 95% CI, 0.80-0.97; P = .01 in non-Europeans and OR = 1.11; 95% CI, 1.02-1.20; P = .02 in Europeans; Pinteraction = 2.73 × 10(-4)). The genotype score, calculated with or without FTO rs9939609, and adjusted for the same covariates, was not associated with depression status.
  
  
  CONCLUSIONS
  Our data support the view that the association between obesity and major depressive disorder at the observational level may be explained, at least in part, by shared genetic factors.
authors.affiliation: Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton General Hospital, McMaster University, Hamilton, Ontario, Canada.|Departments of Clinical Epidemiology and Biostatistics.|Psychiatry and Behavioural Neurosciences.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Samaan
authors.forename: Yvonne K
authors.initials: YK
authors.lastname: Lee
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.forename: James C
authors.initials: JC
authors.lastname: Engert
authors.forename: Jackie
authors.initials: J
authors.lastname: Bosch
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
authors.forename: David
authors.initials: D
authors.lastname: Meyre
mesh_terms: D000328:Adult; D000368:Aged; D044467:American Indian or Alaska Native / Q000235:genetics; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D015992:Body Mass Index; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics