Sex differences in familial risk and genetic components of suicide attempts: a register-based cohort study in Sweden

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Abstract
Background: Suicidal behaviour shows notable sex differences, and understanding whether genetic factors contribute to these differences is critical for identifying at-risk individuals and prevention. Objective: We aim to investigate the genetic contribution to suicide attempts and examine whether genetics account for sex differences in incidence. Methods: This population-based cohort study includes 3.1 million individuals born 1963–1998 and followed through Swedish National Registers, including hospitals and specialist outpatient diagnoses and cause of death data. Suicide attempts were identified using ICD codes, indicating intentional self-harm, self-harm using lethal methods or leading to hospitalisation, or resulting in death. Familial aggregation, coaggregation, pedigree heritability and genetic correlations were estimated using genealogical data. For sex-specific analyses, we examined mother–daughter, female sibling, father–son and male sibling pairs, separately. Findings: Suicide attempts were more common among females than males (3.3% vs 2.6%). In both sexes, risk aggregated within families (ORs ranged 1.6–3.4 across relative types) and was higher in first-degree than second-degree relatives. Familial aggregation was stronger in females than in males, and in same-sex first degree relatives compared with cross-sex pairs. Pedigree heritability was 41.9% (95% CI 36.0 to 48.4%) and did not differ significantly by sex (female 51.4% (95% CI 40.1% to 58.6%), male 45.1% (95% CI 32.3% to 52.5%), Bootstrap p value 0.40). Suicide attempt showed moderate to high pedigree genetic correlations with psychiatric disorders, strongest with substance use disorders (SUD, r g =0.85 (95% CI 0.83 to 0.96)), with no significant sex differences. The genetic correlation between female and male suicide attempts was high (0.85 (95% CI 0.80 to 0.99)), suggesting a substantial genetic overlap. Conclusions: Suicide attempt has a moderate heritable component that largely overlaps between females and males and with other psychiatric disorders, particularly SUD. Stronger familial aggregation in females and in same-sex pairs highlights the potential role of sex-specific environmental or social factors. Future research should focus on non-genetic contributors and their potential interaction with genetic factors to better understand and address sex disparities in suicidal behaviour Clinical implications: Genetic risk for suicide attempt is substantial but does not fully explain sex differences in incidence. Clinicians should, therefore, consider non-genetic, including sex-specific environmental and social factors, alongside family history and psychiatric comorbidity when assessing suicidal risk.
Funding Information
  • European Commission (964874)
  • NordForsk (147386)
  • NordForsk (164218)
  • National Institute of Mental Health (R01MH120170)
  • National Institute of Mental Health (R01MH123724)
  • National Institute of Mental Health (R01MH124871)
  • National Institute of Mental Health (R56MH129437)
  • American Foundation for Suicide Prevention (BSG-0-034-21)
  • American Foundation for Suicide Prevention (DIG-1-037-19)
  • Vetenskapsrådet (2021-02615)
  • Vetenskapsrådet (2022-00126)
  • Vetenskapsrådet (538-2013-8864)
  • Vetenskapsrådet (D0886501)
  • Suicide Prevention Institute at the University of North Carolina, Chapel Hill, NC, USA (N/A)
  • European Research Council (101042183)

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