Gene-environment interactions between CRHR1 variants and physical assault in suicide attempts
Open accessAbstract
Risk factors for suicidal behaviors are partly heritable, including genetic variants that drive diathesis-stress in addition to, or by interaction with, exposure to certain stressful life events (SLEs). Hypothalamic-pituitary-adrenal (HPA) axis regulatory genes are candidates for association with suicide as well as its endophenotypes. Using a family-based design of offspring who attempted suicide (SA) and both parents, we investigated gene-environment interactions (G×Es) of SLE exposures with single nucleotide polymorphisms (SNPs) in corticotropin-releasing hormone receptor-1 (CRHR1), a major HPA axis regulatory gene. We observed a novel G×E among predominantly female SA between 5'-SNP rs7209436 and childhood/adolescence physical assault or attack (PA), as well as a second novel and male-specific G×E between 3'-SNP rs16940665 and adulthood PA exposure. A third male-specific G×E previously reported by us among depressed SA, between SNP rs4792887 and cumulative SLEs, was also further confirmed. The two novel G×Es presented here shared the SA characteristic of aggression, while showing differences on other aspects of SA heterogeneity. We conclude that different SA subjects were observed to differentially associate with two novel G×Es involving exposures to PA with different life timing and SNPs located in opposite ends of CRHR1. Concerning sex differences, we observed three subsets of distinct male SA that associated with each of the three observed G×Es, whereas female SAs were affected by only one of the G×Es. These results are consistent with a diathesis-stress model of suicidal behavior and may help to explain SA heterogeneity.
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Specific CRHR1 polymorphisms interact with ELS/CT to increase the risk of suicide attempts.
“Bradley et al. reported in two separate cohorts, independently, that specific CRHR1 polymorphisms interact with ELS/CT to increase the risk of adult depression (390), similar to Heim et al. (391), while Ben-Efraim et al. (392) reported comparable findings with respect to suicide attempts.”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [392]
The Abstract and the section ‘Identification of two novel G×Es on SA outcome’ report an interaction between CRHR1 rs7209436 and physical assault before age 18 in female suicide attempters. This supports a childhood-adversity interaction, but the paper does not establish that multiple polymorphisms interact with ELS/CT broadly to increase suicide-attempt risk: its other reported interactions concern adult assault or cumulative lifetime stress, and the rs7209436 minor allele had a protective effect. (LLM, conf=0.86)
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“(392) reported comparable findings with respect to suicide attempts.”
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- Authors
- Ben-Efraim, Y. J., Wasserman, D., Wasserman, J., & Sokolowski, M.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Sokolowski, M.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2011-06-09
- Volume
- 10
- Issue
- 6
- Pages
- 663-672
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- OpenAlex
- W2049406343
- Semantic Scholar
- 562c34f7aa45a2f913bd2390107a8b47be1d1f99
- Cited by
- 83
- References
- 58
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 3 · 2019: 7 · 2018: 20 · 2017: 5 · 2016: 9 · 2015: 4 · 2014: 6 · 2013: 7 · 2012: 7
- FWCI
- 6.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes Brain & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Foundation for Suicide Prevention
- Marcus och Amalia Wallenbergs minnesfond
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- suicide attempts, gene-environment interaction, CRHR1, corticotropin-releasing hormone receptor 1, physical assault, life events, hypothalamic-pituitary-adrenal axis, diathesis-stress model, single nucleotide polymorphisms, sex differences, aggression, family-based association
- MeSH terms
- CRF Receptor, Type 1, Adolescent, Adult, Aggression, Depression, Female, Haplotypes, Humans, Life Change Events, Male, Personality, Polymorphism, Genetic, Risk Factors, Sex Factors, Suicide, Attempted, Violence, Receptors, Corticotropin-Releasing Hormone, Genetic Predisposition to Disease, Gene-Environment Interaction
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