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Mapping the genetic architecture of suicide attempt and suicide death using polygenic risk scores for clinically-related psychiatric disorders and traits

Published online by Cambridge University Press:  18 November 2021

Ikuo Otsuka ,
Hanga Galfalvy ,
Jia Guo ,
Masato Akiyama ,
Dan Rujescu ,
Gustavo Turecki ,
Akitoyo Hishimoto  and
J. John Mann
Ikuo Otsuka
Affiliation:
Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan
Hanga Galfalvy
Affiliation:
Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA Department of Biostatistics, Columbia University Mailman School of Public Health, New York, NY, USA
Jia Guo
Affiliation:
Department of Biostatistics, Columbia University Mailman School of Public Health, New York, NY, USA
Masato Akiyama
Affiliation:
Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Dan Rujescu
Affiliation:
Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Gustavo Turecki
Affiliation:
Department of Psychiatry, Douglas Institute, McGill University, Verdun, QC, Canada
Akitoyo Hishimoto*
Affiliation:
Department of Psychiatry, Yokohama City University Graduate School of Medicine, Yokohama, Japan
J. John Mann*
Affiliation:
Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA
*
Author for correspondence: J. John Mann, E-mail: jjm@columbia.edu; Akitoyo Hishimoto, E-mail: hishipon@yokohama-cu.ac.jp
Author for correspondence: J. John Mann, E-mail: jjm@columbia.edu; Akitoyo Hishimoto, E-mail: hishipon@yokohama-cu.ac.jp
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Abstract

Background

Suicidal behavior is moderately heritable and a consequence of a combination of the diathesis traits for suicidal behavior and suicide-related major psychiatric disorders. Here, we sought to examine shared polygenic effects between various psychiatric disorders/traits and suicidal behavior and to compare the shared polygenic effects of various psychiatric disorders/traits on non-fatal suicide attempt and suicide death.

Methods

We used our genotyped European ancestry sample of 260 non-fatal suicide attempters, 317 suicide decedents and 874 non-psychiatric controls to test whether polygenic risk scores (PRSs) obtained from large GWASs for 22 suicide-related psychiatric disorders/traits were associated with suicidal behavior. Results were compared between non-fatal suicide attempt and suicide death in a sensitivity analysis.

Results

PRSs for major depressive disorder, bipolar disorder, schizophrenia, ADHD, alcohol dependence, sensitivity to environmental stress and adversity, educational attainment, cognitive performance, and IQ were associated with suicidal behavior (Bonferroni-corrected p < 2.5 × 10−4). The polygenic effects of all 22 psychiatric disorders/traits had the same direction (p for binomial tests = 4.8 × 10−7) and were correlated (Spearman's ρ = 0.85) between non-fatal suicide attempters and suicide decedents.

Conclusions

We found that polygenic effects for major psychiatric disorders and diathesis-related traits including stress responsiveness and intellect/cognitive function contributed to suicidal behavior. While we found comparable polygenic architecture between non-fatal suicide attempters and suicide decedents based on correlations with PRSs of suicide-related psychiatric disorders/traits, our analyses are limited by small sample size resulting in low statistical power to detect difference between non-fatal suicide attempt and suicide death.

Keywords

Polygenic risk scorepsychiatric disorders and traitssuicide attemptsuicide
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 6 , April 2023 , pp. 2689 - 2697
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally to this work.

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