Mapping the genetic architecture of suicide attempt and suicide death using polygenic risk scores for clinically-related psychiatric disorders and traits
Mapping the genetic architecture of suicide attempt and suicide death using polygenic risk scores for clinically-related psychiatric disorders and traits
复制标题
使用临床相关精神疾病和特征的多基因风险评分绘制自杀未遂和自杀死亡的遗传结构
DOI：
10.1017/s0033291721004700
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发表时间：
2021
影响因子：
6.9
通讯作者：
Mann J. John
中科院分区：
文献类型：
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作者：
Otsuka Ikuo;Galfalvy Hanga;Guo Jia;Akiyama Masato;Rujescu Dan;Turecki Gustavo;Hishimoto Akitoyo;Mann J. John
背景自杀行为是适度遗传的，是自杀行为的素质特征和自杀相关的主要精神障碍相结合的结果。在这里，我们试图研究不同精神障碍/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。方法利用260例非致命性自杀未遂者、317例自杀死亡者和874例非精神对照的欧洲血统样本，检验从大型GWAS获得的22个自杀相关精神障碍/特征的多基因风险评分(PRSS)是否与自杀行为有关。在敏感性分析中比较了非致命性自杀未遂和自杀死亡之间的结果。结果重度抑郁障碍、双相情感障碍、精神分裂症、多动症、酒精依赖、对环境压力和逆境的敏感性、教育程度、认知能力和智商与自杀行为相关(Bonferroni校正p<；2.5×10−4)。所有22种精神障碍/特征的多基因效应具有相同的方向(二项检验的p=4.8×10−7)，并且在非致命性自杀未遂者和自杀死亡者之间存在相关性(Spearman‘sρ=0.85)。结论主要精神障碍和应激反应、智力/认知功能等素质相关特征的多基因效应参与了自杀行为的发生。虽然我们发现非致命性自杀未遂者和自杀死亡者之间基于与自杀相关精神障碍/特征的PRS的相关性而具有相似的多基因结构，但我们的分析受到样本量较小的限制，导致统计能力较低，无法检测非致命性自杀未遂和自杀死亡之间的差异。
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.