New Evidence for the Association of the Serotonin Transporter Gene (SLC6A4) Haplotypes, Threatening Life Events, and Depressive Phenotype

J. Lazáry, Aron Lazary, X. Gonda, Anita Benko, Eszter Molnar, G. Juhász, G. Bagdy

Research output: Contribution to journalArticle

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Abstract

Background: Since the first report of the significant gene-environment interaction (G × E) in depression published by Caspi et al., the literature is considerably contradictory in this field. To clarify this question, we analyzed the interaction between the serotonin transporter gene (SLC6A4) and threatening life events (TLE) on Zung Self-Rating Depression Score (ZSDS). Methods: Five markers tagging the whole SLC6A4 gene (5-HTTLPR and 4 single nucleotide polymorphisms: rs2020942, rs140700, rs3798908, rs1042173) were genotyped in 567 nonclinical individuals. Generalized linear models were used to analyze single marker associations, and likelihood ratio tests and score tests were used for haplotype analysis. Results: Haplotype analysis revealed a significant global effect of haplotypes on ZSDS score in high TLE subgroup (p = .008). Besides the 5-HTTLPR, rs140700 tagging the middle region of the gene had significant effects. Subjects carrying the A allele of rs140700 scored lower on ZSDS independently of 5-HTTLPR carrier status. Explained variances for depressive phenotype were 1%, 4%, and 6% when 5-HTTLPR, 5-HTTLPR × TLE and 5-HTTLPR × rs140700 × TLE were included in the model, respectively. Conclusions: Our results demonstrate heterogeneity of individuals carrying S alleles of 5-HTTLPR in association with high TLE providing possible explanation for the inconsistency of previous studies. In addition to the promoter, the middle region of the SLC6A4 gene carries the G × G × E interaction for mood, and this new model provided a higher explained variance. We report the first evidence for the significant effects of haplotypes of the SLC6A4 gene and threatening life events on depressive phenotype.

Original languageEnglish
Pages (from-to)498-504
Number of pages7
JournalBiological Psychiatry
Volume64
Issue number6
DOIs
Publication statusPublished - Sep 15 2008

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Haplotypes
Phenotype
Depression
Genes
Gene-Environment Interaction
Alleles
Genetic Promoter Regions
Single Nucleotide Polymorphism
Linear Models

Keywords

  • 5-HTTLPR
  • Depression
  • G × E interaction
  • haplotype analysis
  • polymorphism
  • threatening life events

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

New Evidence for the Association of the Serotonin Transporter Gene (SLC6A4) Haplotypes, Threatening Life Events, and Depressive Phenotype. / Lazáry, J.; Lazary, Aron; Gonda, X.; Benko, Anita; Molnar, Eszter; Juhász, G.; Bagdy, G.

In: Biological Psychiatry, Vol. 64, No. 6, 15.09.2008, p. 498-504.

Research output: Contribution to journalArticle

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abstract = "Background: Since the first report of the significant gene-environment interaction (G × E) in depression published by Caspi et al., the literature is considerably contradictory in this field. To clarify this question, we analyzed the interaction between the serotonin transporter gene (SLC6A4) and threatening life events (TLE) on Zung Self-Rating Depression Score (ZSDS). Methods: Five markers tagging the whole SLC6A4 gene (5-HTTLPR and 4 single nucleotide polymorphisms: rs2020942, rs140700, rs3798908, rs1042173) were genotyped in 567 nonclinical individuals. Generalized linear models were used to analyze single marker associations, and likelihood ratio tests and score tests were used for haplotype analysis. Results: Haplotype analysis revealed a significant global effect of haplotypes on ZSDS score in high TLE subgroup (p = .008). Besides the 5-HTTLPR, rs140700 tagging the middle region of the gene had significant effects. Subjects carrying the A allele of rs140700 scored lower on ZSDS independently of 5-HTTLPR carrier status. Explained variances for depressive phenotype were 1{\%}, 4{\%}, and 6{\%} when 5-HTTLPR, 5-HTTLPR × TLE and 5-HTTLPR × rs140700 × TLE were included in the model, respectively. Conclusions: Our results demonstrate heterogeneity of individuals carrying S alleles of 5-HTTLPR in association with high TLE providing possible explanation for the inconsistency of previous studies. In addition to the promoter, the middle region of the SLC6A4 gene carries the G × G × E interaction for mood, and this new model provided a higher explained variance. We report the first evidence for the significant effects of haplotypes of the SLC6A4 gene and threatening life events on depressive phenotype.",
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AU - Gonda, X.

AU - Benko, Anita

AU - Molnar, Eszter

AU - Juhász, G.

AU - Bagdy, G.

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AB - Background: Since the first report of the significant gene-environment interaction (G × E) in depression published by Caspi et al., the literature is considerably contradictory in this field. To clarify this question, we analyzed the interaction between the serotonin transporter gene (SLC6A4) and threatening life events (TLE) on Zung Self-Rating Depression Score (ZSDS). Methods: Five markers tagging the whole SLC6A4 gene (5-HTTLPR and 4 single nucleotide polymorphisms: rs2020942, rs140700, rs3798908, rs1042173) were genotyped in 567 nonclinical individuals. Generalized linear models were used to analyze single marker associations, and likelihood ratio tests and score tests were used for haplotype analysis. Results: Haplotype analysis revealed a significant global effect of haplotypes on ZSDS score in high TLE subgroup (p = .008). Besides the 5-HTTLPR, rs140700 tagging the middle region of the gene had significant effects. Subjects carrying the A allele of rs140700 scored lower on ZSDS independently of 5-HTTLPR carrier status. Explained variances for depressive phenotype were 1%, 4%, and 6% when 5-HTTLPR, 5-HTTLPR × TLE and 5-HTTLPR × rs140700 × TLE were included in the model, respectively. Conclusions: Our results demonstrate heterogeneity of individuals carrying S alleles of 5-HTTLPR in association with high TLE providing possible explanation for the inconsistency of previous studies. In addition to the promoter, the middle region of the SLC6A4 gene carries the G × G × E interaction for mood, and this new model provided a higher explained variance. We report the first evidence for the significant effects of haplotypes of the SLC6A4 gene and threatening life events on depressive phenotype.

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