title: Serotonin 1A receptor gene and major depressive disorder: an association study and meta-analysis.
abstract: Several genetic studies have shown an association between the 5-HT1A receptor gene (HTR1A) and major depressive disorder (MDD); however, results have been rather inconsistent. Moreover, to our knowledge, no association study on HTR1A and MDD in the Japanese population has been reported. Therefore, to evaluate the association between HTR1A and MDD, we conducted a case-control study of Japanese population samples with two single-nucleotide polymorphisms (SNPs), including rs6295 (C-1019G) in HTR1A. In addition, we conducted a meta-analysis of rs6295, which has been examined in other papers. Using one functional SNP (rs6295) and one tagging SNP (rs878567) selected with the HapMap database, we conducted a genetic association analysis of case-control samples (331 patients with MDD and 804 controls) in the Japanese population. Seven population-based association studies, including this study, met our criteria for the meta-analysis of rs6295. We found an association between rs878567 and Japanese MDD patients in the allele-wise analysis, but the significance of this association did not remain after Bonferroni's correction. We also did not detect any association between HTR1A and MDD in the allele/genotype-wise or haplotype-wise analysis. On the other hand, we detected an association between rs6295 and MDD in the meta-analysis (P(Z)=0.0327). In an explorative analysis, rs6295 was associated with Asian MDD patients after correction for multiple testing (P(Z)=0.0176), but not with Caucasian MDD patients (P(Z)=0.138). Our results suggest that HTR1A may not have a role in the pathophysiology of Japanese MDD patients. On the other hand, according to the meta-analysis, HTR1A was associated with MDD patients, especially in the Asian population.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. tarok@fujita-hu.ac.jp
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsunoka
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Kawashima
authors.forename: Tomo
authors.initials: T
authors.lastname: Okochi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kitajima
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Takenori
authors.initials: T
authors.lastname: Okumura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamanouchi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*
chemical_list: D044282:Receptor, Serotonin, 5-HT1A