{
  "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 behaviourClinical 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.",
  "authors": [
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Thuy-Dung Nguyen"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Tong Gong"
    },
    {
      "affiliations": [
        "Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden",
        "Sleep Medicine Center, Mental Health Center, Sleep Medicine Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China",
        "West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Kejia Hu"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Ralf Kuja-Halkola"
    },
    {
      "affiliations": [
        "Division of Psychiatry, University of Edinburg, Edinburgh, UK",
        "Department of Psychiatry, Mayo Clinic, Rochester, New York, USA"
      ],
      "name": "Karen Borges"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden",
        "Division of Mental Health Services, Akershus University Hospital, Lørenskog, Norway",
        "Institute of Clinical Medicine, University of Oslo, Oslo, Norway",
        "Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland"
      ],
      "name": "Agnieszka Butwicka"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden",
        "Global Public Health and Primary Care, University of Bergen, Bergen, Norway",
        "Department of Biomedicine, Aarhus University, Aarhus, Denmark"
      ],
      "name": "Isabell Brikell"
    },
    {
      "affiliations": [
        "Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA",
        "Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA",
        "Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "James J Crowley"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Zheng Chang"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden",
        "Department of Psychological, Indiana University Bloomington, Bloomington, Indiana, USA"
      ],
      "name": "Brian M D’Onofrio"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden",
        "School of Medical Sciences, Örebro universitet, Örebro, Sweden"
      ],
      "name": "Henrik Larsson"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Paul Lichtenstein"
    },
    {
      "affiliations": [
        "Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden",
        "Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden"
      ],
      "name": "Christian Rück"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden",
        "Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA",
        "Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"
      ],
      "name": "Cynthia Bulik"
    },
    {
      "affiliations": [
        "Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Fang Fang"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden",
        "Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA",
        "Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"
      ],
      "name": "Patrick Sullivan"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Yi Lu"
    }
  ],
  "title": "Sex differences in familial risk and genetic components of suicide attempts: a register-based cohort study in Sweden",
  "uid": "fea8e8c0-194c-53cf-8cbf-6df60a266973"
}