Genetic Relationships Between Suicide Attempts, Suicidal Ideation and Major Psychiatric Disorders: A Genome-Wide Association and Polygenic Scoring Study
Genetic Relationships Between Suicide Attempts, Suicidal Ideation and Major Psychiatric Disorders: A Genome-Wide Association and Polygenic Scoring Study
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DOI：
10.1002/ajmg.b.32247
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发表时间：
2014-07-01
影响因子：
2.8
通讯作者：
Lewis, Cathryn M.
中科院分区：
文献类型：
--
作者：
Mullins, Niamh;Perroud, Nader;Lewis, Cathryn M.
流行病学研究已经认识到自杀行为的遗传素质，这是独立于其他精神疾病。关于自杀企图（SA）和意念的全基因组关联研究（GWAS）未能确定特定的遗传变异。在这里，我们进行了进一步的GWAS，并首次在心境障碍患者队列中使用多基因评分分析，以测试心境障碍和自杀表型的常见遗传变异。在RADIANT和GSK-慕尼黑复发性抑郁症样本和伦敦双相情感障碍病例对照研究（BACCs）中进行SA的全基因组研究，然后进行荟萃分析。先前在基于基因组的抑郁症治疗药物（GENDEP）研究中进行了关于抗抑郁药治疗期间自杀意念的GWAS。我们从每个样本中获得多基因评分，并在GENDEP研究中测试其预测情绪障碍队列或思维状态中SA的能力。来自精神病学基因组学联盟的重性抑郁症、双相情感障碍和精神分裂症的多基因评分被用于研究精神疾病和自杀表型之间的多效性。在GWAS或荟萃分析中，在任何SNP处均未检测到相关性的显著证据。在GENDEP药物遗传学研究中，重度抑郁症的多基因评分可显著预测自杀意念，在联合验证数据集中也可预测SA。SA的多基因评分显示对自杀意念无预测能力。多基因评分分析表明精神疾病和自杀想法之间存在多效性，而对此类想法采取行动的倾向可能具有部分独立的遗传素质。(C)2014 Wiley Periodicals，Inc.
Epidemiological studies have recognized a genetic diathesis for suicidal behavior, which is independent of other psychiatric disorders. Genome-wide association studies (GWAS) on suicide attempt (SA) and ideation have failed to identify specific genetic variants. Here, we conduct further GWAS and for the first time, use polygenic score analysis in cohorts of patients with mood disorders, to test for common genetic variants for mood disorders and suicide phenotypes. Genome-wide studies for SA were conducted in the RADIANT and GSK-Munich recurrent depression samples and London Bipolar Affective Disorder Case-Control Study (BACCs) then meta-analysis was performed. A GWAS on suicidal ideation during antidepressant treatment had previously been conducted in the Genome Based Therapeutic Drugs for Depression (GENDEP) study. We derived polygenic scores from each sample and tested their ability to predict SA in the mood disorder cohorts or ideation status in the GENDEP study. Polygenic scores for major depressive disorder, bipolar disorder and schizophrenia from the Psychiatric Genomics Consortium were used to investigate pleiotropy between psychiatric disorders and suicide phenotypes. No significant evidence for association was detected at any SNP in GWAS or meta-analysis. Polygenic scores for major depressive disorder significantly predicted suicidal ideation in the GENDEP pharmacogenetics study and also predicted SA in a combined validation dataset. Polygenic scores for SA showed no predictive ability for suicidal ideation. Polygenic score analysis suggests pleiotropy between psychiatric disorders and suicidal ideation whereas the tendency to act on such thoughts may have a partially independent genetic diathesis. (C) 2014 Wiley Periodicals, Inc.