Bipolar disorder (BD) is associated with a 20–30-fold increased suicide risk compared to the general population. First-degree relatives of BD patients show inflated rates of psychopathology including suicidal behaviors. As reliable biomarkers of suicide attempts (SA) are lacking, we examined associations between suicide-related polygenic risk scores (PRSs)—a quantitative index of genomic risk—and variability in brain structures implicated in SA. Participants (n = 206; aged 12–30 years) were unrelated individuals of European ancestry and comprised three groups: 41 BD cases, 96 BD relatives (“high risk”), and 69 controls. Genotyping employed PsychArray, followed by imputation. Three PRSs were computed using genome-wide association data for SA in BD (SA-in-BD), SA in major depressive disorder (SA-in-MDD) (Mullins et al., 2019, The American Journal of Psychiatry, 176(8), 651–660), and risky behavior (Karlsson Linnér et al., 2019, Nature Genetics, 51(2), 245–257). Structural magnetic resonance imaging processing employed FreeSurfer v5.3.0. General linear models were constructed using 32 regions-of-interest identified from suicide neuroimaging literature, with false-discovery-rate correction. SA-in-MDD and SA-in-BD PRSs negatively predicted parahippocampal thickness, with the latter association modified by group membership. SA-in-BD and Risky Behavior PRSs inversely predicted rostral and caudal anterior cingulate structure, respectively, with the latter effect driven by the “high risk” group. SA-in-MDD and SA-in-BD PRSs positively predicted cuneus structure, irrespective of group. This study demonstrated associations between PRSs for suicide-related phenotypes and structural variability in brain regions implicated in SA. Future exploration of extended PRSs, in conjunction with a range of biological, phenotypic, environmental, and experiential data in high risk populations, may inform predictive models for suicidal behaviors.

中文翻译：

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自杀未遂和危险行为的多基因风险对有双相情感障碍家族风险的年轻人大脑结构的影响

与普通人群相比，双相情感障碍 (BD) 的自杀风险增加 20-30 倍。BD 患者的一级亲属表现出包括自杀行为在内的精神病理学比率过高。由于缺乏可靠的自杀未遂 (SA) 生物标志物，我们检查了与自杀相关的多基因风险评分 (PRS) - 基因组风险的定量指标 - 与涉及 SA 的大脑结构变异性之间的关联。参与者（n = 206; 年龄 12-30 岁）是与欧洲血统无关的个体，包括三组：41 名 BD 病例、96 名 BD 亲属（“高风险”）和 69 名对照。基因分型采用 PsychArray，然后是插补。使用 BD 中的 SA (SA-in-BD)、重度抑郁症中的 SA (SA-in-MDD) 的全基因组关联数据计算了三个 PRS（Mullins 等人，2019 年，美国精神病学杂志，176（ 8), 651–660) 和危险行为 (Karlsson Linnér 等人, 2019, Nature Genetics , 51(2), 245–257)。结构磁共振成像处理采用FreeSurfer v5.3.0。使用从自杀神经影像学文献中确定的 32 个感兴趣区域构建一般线性模型，并进行错误发现率校正。SA-in-MDD 和 SA-in-BD PRS 对海马旁厚度有负预测作用，后者的关联由组成员资格修改。SA-in-BD 和危险行为 PRS 分别反向预测头端和尾端前扣带回结构，后一种效应由“高风险”组驱动。SA-in-MDD 和 SA-in-BD PRS 正向预测楔叶结构，与组无关。这项研究证明了自杀相关表型的 PRS 与涉及 SA 的大脑区域的结构变异性之间的关联。扩展 PRS 的未来探索，