title: Effects of corticotropin-releasing hormone receptor 1 SNPs on major depressive disorder are influenced by sex and smoking status.
abstract: The corticotropin-releasing hormone receptor 1 (CRHR1) gene has been repeatedly implicated in Major Depressive Disorder (MDD) in humans and animal models; however, the findings are not absolutely convergent. Since recent evidence from genome-wide association studies suggests that narrowing the phenotypic heterogeneity may be crucial in genetic studies of MDD, the aim of this study was to evaluate the effects of CRHR1 polymorphisms on MDD while addressing the influence of sex and smoking status.
  
  
  
  The association of the CRHR1 SNPs rs12944712, rs110402, and rs878886 with MDD was evaluated in 629 Brazilian adults of European descent recruited from the general population [180 (28.6%) with lifetime MDD]. The sample was subdivided according to sex and smoking status RESULTS: Among nonsmokers, there were nominal associations between MDD and all tested SNPs (rs12944712, P=0.042; rs110402, P=0.031, and rs878886, P=0.040), regardless of sex. In addition, there were significant effects of rs110402 in women (Pcorr=0.034) and rs878886 in men (Pcorr=0.013). Among lifetime smokers, there were no significant associations between CRHR1 SNPs and MDD LIMITATIONS: The lack of a depression rating scale; scarcity of information on the functionality of the CRHR1 SNPs; and relatively small sample sizes in some subgroups.
  
  
  
  Our results strengthen the evidence for the role of CRHR1 SNPs in MDD susceptibility and suggest that their effects may be modulated by sex and smoking status. These findings suggest the perspective that reducing phenotypic heterogeneity is warranted in genetic studies of MDD.
authors.affiliation: Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Bruna S
authors.initials: BS
authors.lastname: da Silva
authors.affiliation: Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Diego L
authors.initials: DL
authors.lastname: Rovaris
authors.affiliation: Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Jaqueline B
authors.initials: JB
authors.lastname: Schuch
authors.affiliation: Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Nina R
authors.initials: NR
authors.lastname: Mota
authors.affiliation: Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Renata B
authors.initials: RB
authors.lastname: Cupertino
authors.affiliation: Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Angelita P
authors.initials: AP
authors.lastname: Aroche
authors.affiliation: Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Guilherme P
authors.initials: GP
authors.lastname: Bertuzzi
authors.affiliation: ADHD Outpatient Program, Adult Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Rafael G
authors.initials: RG
authors.lastname: Karam
authors.affiliation: ADHD Outpatient Program, Adult Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Eduardo S
authors.initials: ES
authors.lastname: Vitola
authors.affiliation: Postgraduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Tovo-Rodrigues
authors.affiliation: ADHD Outpatient Program, Adult Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Department of Psychiatry, Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Eugenio H
authors.initials: EH
authors.lastname: Grevet
authors.affiliation: Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; ADHD Outpatient Program, Adult Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. Electronic address: claiton.bau@ufrgs.br.
authors.forename: Claiton H D
authors.initials: CH
authors.lastname: Bau
mesh_terms: D000328:Adult; D001938:Brazil; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D044465:White People; D055815:Young Adult; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1
keywords: CRHR1; Depression; Gender; Genetics; Smoking; Stress