利用与临床相关的精神障碍和特征的多基因风险评分来绘制自杀未遂和自杀死亡的遗传结构。
Mapping the genetic architecture of suicide attempt and suicide death using polygenic risk scores for clinically-related psychiatric disorders and traits.
机构信息
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.
出版信息
Psychol Med. 2023 Apr;53(6):2689-2697. doi: 10.1017/S0033291721004700. Epub 2021 Nov 18.
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 < 2.5 × 10). The polygenic effects of all 22 psychiatric disorders/traits had the same direction ( for binomial tests = 4.8 × 10) and were correlated (Spearman's = 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.
背景
自杀行为具有中等程度的遗传性，是自杀行为和与自杀相关的主要精神障碍的素质特征共同作用的结果。在这里，我们试图研究各种精神障碍/特征与自杀行为之间的共同多基因效应，并比较各种精神障碍/特征对非致命性自杀未遂和自杀死亡的共同多基因效应。
方法
我们使用经过基因分型的欧洲血统样本，其中包括 260 名非致命性自杀未遂者、317 名自杀死者和 874 名非精神科对照者，以检验从 22 种与自杀相关的精神障碍/特征的大型 GWAS 中获得的多基因风险评分（PRS）是否与自杀行为相关。在一项敏感性分析中，我们比较了非致命性自杀未遂和自杀死亡之间的结果。
结果
PRS 与重度抑郁症、双相情感障碍、精神分裂症、ADHD、酒精依赖、对环境压力和逆境的敏感性、受教育程度、认知表现和智商相关（Bonferroni 校正 < 2.5×10）。所有 22 种精神障碍/特征的多基因效应具有相同的方向（二项式检验= 4.8×10），且在非致命性自杀未遂者和自杀死者之间存在相关性（Spearman's = 0.85）。
结论
我们发现，主要精神障碍的多基因效应以及与素质相关的特征，包括应激反应性和智力/认知功能，与自杀行为有关。虽然我们根据与自杀相关的精神障碍/特征的 PRS 的相关性，发现非致命性自杀未遂者和自杀死者之间存在相似的多基因结构，但我们的分析受到小样本量的限制，导致检测非致命性自杀未遂和自杀死亡之间差异的统计能力较低。
Zotero 插件