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

Annette Erlangsen; Vivek Appadurai; Yunpeng Wang; Gustavo Turecki; Ole Mors; Thomas Werge; Preben B Mortensen; Anna Starnawska; Anders D Børglum; Andrew Schork; Ron Nudel; Marie Bækvad-Hansen; Jonas Bybjerg-Grauholm; David M Hougaard; Wesley K Thompson; Merete Nordentoft; Esben Agerbo

doi:10.1038/s41380-018-0218-y

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

Annette Erlangsen, Vivek Appadurai, Yunpeng Wang, Gustavo Turecki, Ole Mors, Thomas Werge, Preben B Mortensen, Anna Starnawska, Anders D Børglum, Andrew Schork, Ron Nudel, Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm, David M Hougaard, Wesley K Thompson, Merete Nordentoft, Esben Agerbo

Department of Clinical Medicine

29 Citations (Scopus)

Abstract

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 language	English
Journal	Molecular Psychiatry
ISSN	1359-4184
DOIs	https://doi.org/10.1038/s41380-018-0218-y
Publication status	Published - 1 Oct 2020

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Erlangsen, A., Appadurai, V., Wang, Y., Turecki, G., Mors, O., Werge, T., Mortensen, P. B., Starnawska, A., Børglum, A. D., Schork, A., Nudel, R., Bækvad-Hansen, M., Bybjerg-Grauholm, J., Hougaard, D. M., Thompson, W. K., Nordentoft, M., & Agerbo, E. (2020). Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study. Molecular Psychiatry. https://doi.org/10.1038/s41380-018-0218-y

Erlangsen, A, Appadurai, V, Wang, Y, Turecki, G, Mors, O, Werge, T, Mortensen, PB, Starnawska, A, Børglum, AD, Schork, A, Nudel, R, Bækvad-Hansen, M, Bybjerg-Grauholm, J, Hougaard, DM, Thompson, WK, Nordentoft, M & Agerbo, E 2020, 'Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study', Molecular Psychiatry. https://doi.org/10.1038/s41380-018-0218-y

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abstract = "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.",

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AU - Erlangsen, Annette

AU - Appadurai, Vivek

AU - Wang, Yunpeng

AU - Turecki, Gustavo

AU - Mors, Ole

AU - Werge, Thomas

AU - Mortensen, Preben B

AU - Starnawska, Anna

AU - Børglum, Anders D

AU - Schork, Andrew

AU - Nudel, Ron

AU - Bækvad-Hansen, Marie

AU - Bybjerg-Grauholm, Jonas

AU - Hougaard, David M

AU - Thompson, Wesley K

AU - Nordentoft, Merete

AU - Agerbo, Esben

PY - 2020/10/1

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N2 - 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.

AB - 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.

U2 - 10.1038/s41380-018-0218-y

DO - 10.1038/s41380-018-0218-y

M3 - Journal article

C2 - 30116032

SN - 1359-4184

JO - Molecular Psychiatry

JF - Molecular Psychiatry

ER -

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

Abstract

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