Genetic and environmental determinants of violence risk in psychotic disorders: a multivariate quantitative genetic study of 1.8 million Swedish twins and siblings.
Genetic and environmental determinants of violence risk in psychotic disorders: a multivariate quantitative genetic study of 1.8 million Swedish twins and siblings.
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DOI：
10.1038/mp.2015.184
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发表时间：
2016-09
影响因子：
11
通讯作者：
Fazel S
中科院分区：
文献类型：
--
作者：
Sariaslan A;Larsson H;Fazel S
被诊断为精神障碍（例如，精神分裂症和双相情感障碍）的患者实施暴力行为的风险增加，特别是如果他们与药物滥用共病。尽管最近的定量和分子遗传学研究的见解，这些表型的遗传结构表现出相当大的多效性，目前缺乏大规模的研究，专门研究精神障碍和暴力之间的病因联系。使用样本的所有瑞典人出生于1958年和1989年之间（n=3 332 101），我们确定了共923 259双胞胎兄弟姐妹对。使用基于国际疾病分类（ICD）8-10的经验证算法，使用国家患者登记册识别患者。单变量定量遗传模型显示，所有的表型（精神分裂症，双相情感障碍，物质滥用和暴力犯罪）是高度遗传（h2=53-71%）。多变量模型进一步显示，精神分裂症是一个更强的预测暴力（r=0.32; 95%置信区间：0.30-0.33）比双相情感障碍（r=0.23; 0.21-0.25），这些表型相关性的大部分（51-67%）解释了遗传因素之间共享的每种疾病，物质滥用，和暴力。重要的是，我们发现，与药物滥用无关的遗传影响解释了双相情感障碍与暴力犯罪的大约五分之一（21% 20-22%）的相关性，但在精神分裂症中没有相同的相关性（P <0.001; P精神分裂症=0.55）。这些发现突出了在遗传相似的表型中没有解开共同和独特的协方差来源的问题，因为后者的来源可能包括病因学上重要的线索。在临床上，这些发现强调了评估不同表型的风险以及整合精神疾病，药物滥用和暴力干预的重要性。
Patients diagnosed with psychotic disorders (for example, schizophrenia and bipolar disorder) have elevated risks of committing violent acts, particularly if they are comorbid with substance misuse. Despite recent insights from quantitative and molecular genetic studies demonstrating considerable pleiotropy in the genetic architecture of these phenotypes, there is currently a lack of large-scale studies that have specifically examined the aetiological links between psychotic disorders and violence. Using a sample of all Swedish individuals born between 1958 and 1989 (n=3 332 101), we identified a total of 923 259 twin-sibling pairs. Patients were identified using the National Patient Register using validated algorithms based on International Classification of Diseases (ICD) 8–10. Univariate quantitative genetic models revealed that all phenotypes (schizophrenia, bipolar disorder, substance misuse, and violent crime) were highly heritable (h2=53–71%). Multivariate models further revealed that schizophrenia was a stronger predictor of violence (r=0.32; 95% confidence interval: 0.30–0.33) than bipolar disorder (r=0.23; 0.21–0.25), and large proportions (51–67%) of these phenotypic correlations were explained by genetic factors shared between each disorder, substance misuse, and violence. Importantly, we found that genetic influences that were unrelated to substance misuse explained approximately a fifth (21% 20–22%) of the correlation with violent criminality in bipolar disorder but none of the same correlation in schizophrenia (Pbipolar disorder<0.001; Pschizophrenia=0.55). These findings highlight the problems of not disentangling common and unique sources of covariance across genetically similar phenotypes as the latter sources may include aetiologically important clues. Clinically, these findings underline the importance of assessing risk of different phenotypes together and integrating interventions for psychiatric disorders, substance misuse, and violence.