Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study

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  • Annette Erlangsen, Danish Research Institute for Suicide Prevention, Mental Health Centre Copenhagen, Copenhagen, Denmark. Annette.Erlangsen@regionh.dk., Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Annette.Erlangsen@regionh.dk., Center of Mental Health Research, Australian National University, Canberra, Australia. Annette.Erlangsen@regionh.dk., iPSYCH The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Denmark
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  • Vivek Appadurai, Institute of Biological Psychiatry, Sct. Hans Mental Health Center, Copenhagen Mental Health Services, iPSYCH - The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, Boserupvej, DK-4000, Roskilde, Denmark.
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  • Yunpeng Wang, K. G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway ; Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
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  • Gustavo Turecki, McGill Group for Suicide Studies, Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Canada.
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  • Ole Mors
  • Thomas Werge, Institute of Clinical Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark., The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH,Denmark.
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  • Preben B Mortensen
  • Anna Starnawska
  • Anders D Børglum
  • Andrew Schork, Institute of Biological Psychiatry, Sct. Hans Mental Health Center, Copenhagen Mental Health Services, iPSYCH - The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, Boserupvej, DK-4000, Roskilde, Denmark.
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  • Ron Nudel, Institute of Biological Psychiatry, Sct. Hans Mental Health Center, Copenhagen Mental Health Services, iPSYCH - The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, Boserupvej, DK-4000, Roskilde, Denmark.
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  • Marie Bækvad-Hansen, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • Jonas Bybjerg-Grauholm, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • David M Hougaard, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • Wesley K Thompson, Division of Biostatistics, Department of Family Medicine and Public Health, University of California, San Diego, CA, USA.
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  • Merete Nordentoft, 1Psychiatric Research Unit,Mental Health Centre Copenhagen,Copenhagen University Hospital,Bispebjerg,Copenhagen,NV,Denmark.
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  • Esben Agerbo

Family studies have shown an aggregation of suicidal behavior in families. Yet, molecular studies are needed to identify loci accounting for genetic heritability. We conducted a genome-wide association study and estimated single nucleotide polymorphisms (SNP) heritability for a suicide attempt. In a case-cohort study, national data on all individuals born in Denmark after 1981 and diagnosed with severe mental disorders prior to 2013 (n = 57,377) and individuals from the general population (n = 30,000) were obtained. After quality control, the sample consisted of 6024 cases with an incidence of suicide attempt and 44,240 controls with no record of a suicide attempt. Suggestive associations between SNPs, rs6880062 (p-value: 5.4 × 10-8) and rs6880461 (p-value: 9.5 × 10-8), and suicide attempt were identified when adjusting for socio-demographics. Adjusting for mental disorders, three significant associations, all on chromosome 20, were identified: rs4809706 (p-value: 2.8 × 10-8), rs4810824 (p-value: 3.5 × 10-8), and rs6019297 (p-value: 4.7 × 108). Sub-group analysis of cases with affective disorders revealed SNPs associated with suicide attempts when compared to the general population for gene PDE4B. All SNPs explained 4.6% [CI-95: 2.9-6.3%] of the variation in suicide attempt. Controlling for mental disorders reduced the heritability to 1.9% [CI-95: 0.3-3.5%]. Affective and autism spectrum disorders exhibited a SNP heritability of 5.6% [CI-95: 1.9-9.3%] and 9.6% [CI-95: 1.1-18.1%], respectively. Using the largest sample to date, we identified significant SNP associations with suicide attempts and support for a genetic transmission of suicide attempt, which might not solely be explained by mental disorders.

Original languageEnglish
JournalMolecular Psychiatry
ISSN1359-4184
DOIs
Publication statusE-pub ahead of print - 16 Aug 2018

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