Serotonin 1A receptor gene and major depressive disorder: An association study and meta-analysis

Taro Kishi, Tomoko Tsunoka, Masashi Ikeda, Kunihiro Kawashima, Tomo Okochi, Tsuyoshi Kitajima, Yoko Kinoshita, Takenori Okumura, Yoshio Yamanouchi, Toshiya Inada, Norio Ozaki, Nakao Iwata

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)629-633
Number of pages5
JournalJournal of Human Genetics
Volume54
Issue number11
DOIs
Publication statusPublished - 01-11-2009

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Receptor, Serotonin, 5-HT1A
Major Depressive Disorder
Meta-Analysis
Genes
Single Nucleotide Polymorphism
Population
Alleles
HapMap Project
Haplotypes
Case-Control Studies
Genotype
Databases

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Kishi, Taro ; Tsunoka, Tomoko ; Ikeda, Masashi ; Kawashima, Kunihiro ; Okochi, Tomo ; Kitajima, Tsuyoshi ; Kinoshita, Yoko ; Okumura, Takenori ; Yamanouchi, Yoshio ; Inada, Toshiya ; Ozaki, Norio ; Iwata, Nakao. / Serotonin 1A receptor gene and major depressive disorder : An association study and meta-analysis. In: Journal of Human Genetics. 2009 ; Vol. 54, No. 11. pp. 629-633.
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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.",
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Kishi, T, Tsunoka, T, Ikeda, M, Kawashima, K, Okochi, T, Kitajima, T, Kinoshita, Y, Okumura, T, Yamanouchi, Y, Inada, T, Ozaki, N & Iwata, N 2009, 'Serotonin 1A receptor gene and major depressive disorder: An association study and meta-analysis', Journal of Human Genetics, vol. 54, no. 11, pp. 629-633. https://doi.org/10.1038/jhg.2009.84

Serotonin 1A receptor gene and major depressive disorder : An association study and meta-analysis. / Kishi, Taro; Tsunoka, Tomoko; Ikeda, Masashi; Kawashima, Kunihiro; Okochi, Tomo; Kitajima, Tsuyoshi; Kinoshita, Yoko; Okumura, Takenori; Yamanouchi, Yoshio; Inada, Toshiya; Ozaki, Norio; Iwata, Nakao.

In: Journal of Human Genetics, Vol. 54, No. 11, 01.11.2009, p. 629-633.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Serotonin 1A receptor gene and major depressive disorder

T2 - An association study and meta-analysis

AU - Kishi, Taro

AU - Tsunoka, Tomoko

AU - Ikeda, Masashi

AU - Kawashima, Kunihiro

AU - Okochi, Tomo

AU - Kitajima, Tsuyoshi

AU - Kinoshita, Yoko

AU - Okumura, Takenori

AU - Yamanouchi, Yoshio

AU - Inada, Toshiya

AU - Ozaki, Norio

AU - Iwata, Nakao

PY - 2009/11/1

Y1 - 2009/11/1

N2 - 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.

AB - 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.

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