Association between TPH1 polymorphisms and the risk of suicide behavior: an updated meta-analysis of 18,398 individuals
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Objectives We aimed to examine the association ofTPH1polymorphisms with the risk of suicide behavior (SB). Design Systematic review and meta-analysis. Method All relevant studies that evaluated the association between the A218C (rs1800532), A779C (rs1799913) and A6526G (rs4537731) polymorphisms and the susceptibility to SB published up to September 2021 were identified through a comprehensive systematic search in PubMed, Scopus, EBSCO and Science Direct electronic databases. The association betweenTPH1gene polymorphisms and SB was evaluated using inherence models by odds ratio (OR) and 95% confidence interval (CI). Subgroup analyses, heterogeneity analyses, and publication bias were also tested in this meta-analysis. Results The meta-analysis forTPH1A218C revealed an increased risk of SB in the dominant model (OR = 1.11, 95%CI 1.01–1.22). We also observed a positive association in the allelic (OR = 1.13, 95%CI 1.05–1.21), homozygous (OR = 1.22, 95%CI 1.06–1.40), heterozygous (OR = 1.21, 95%CI 1.08–1.37) and dominant (OR = 1.21, 95%CI 1.09–1.34) inherence models with the suicide attempt. Additionally, in the heterozygous (OR = 0.84, 95%CI 0.73–0.97) and dominant (OR = 0.79, 95%CI 0.68–0.91) inherence models we detected an association with completed suicide. Based on ethnicity, an association of SB in the European population also was observed (OR = 1.29, 95%CI 1.12–1.51). However, for both A779C and A6526G polymorphisms we did not find evidence of an association with SB. Conclusion This meta-analysis suggests that the A218C polymorphism ofTPH1gene could be a possible risk factor of SB. Future large-scale studies are required to analyze the molecular mechanisms by which affect the susceptibility of developing suicide behavior.
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Variants in tryptophan hydroxylase (TPH1, TPH2), serotonin transporter (5-HTTLPR), and serotonin receptors (5-HTR1A, 5-HTR2A) have been associated with suicidal behaviors in adults, though replication in pediatric cohorts remains limited.
“Variants in tryptophan hydroxylase (TPH1, TPH2), serotonin transporter (5-HTTLPR), and serotonin receptors (5-HTR1A, 5-HTR2A) have been associated with suicidal behaviors in adults, though replication in pediatric cohorts remains limited (44, 45).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [44]
The Results (TPH1 A218C polymorphism and the risk of SB; page unavailable) report an association between one TPH1 variant and suicidal behavior. The paper does not establish the claimed associations for TPH2, 5-HTTLPR, 5-HTR1A, or 5-HTR2A, or state that replication in pediatric cohorts is limited. Its study-characteristics section gives an age range of 17.4–65 years, so the pooled evidence is not exclusively adult. (LLM, conf=0.88)
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- Authors
- Genis-Mendoza, A. D., Hernández-Díaz, Y., González-Castro, T. B., Tovilla-Zárate, C. A., Castillo-Avila, R. G., López-Narváez, M. L., Ramos-Méndez, M. Á., & Nicolini, H.
- Affiliations
- Universidad Juárez Autónoma de Tabasco (MX)
- National Institute of Genomic Medicine (MX)
- Corresponding author
- Nicolini, Humberto
- ORCID
- Nicolini, Humberto
- Venue
- Frontiers in Psychiatry
- Publisher
- Frontiers Media SA
- Published
- 2022-07-19
- Volume
- 13
- Pages
- 932135-932135
- ISSN
- 1664-0640 (ISSN-L)
- PMC
- PMC9343722
- OpenAlex
- W4285796564
- Cited by
- 5
- References
- 55
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1
- FWCI
- 0.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- tryptophan hydroxylase 1, tryptophan hydroxylase, suicidal behavior, suicide attempts, suicide mortality, genetic susceptibility
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