Association of Genetic Risk Factors for Psychiatric Disorders and Traits of These Disorders in a Swedish Population Twin Sample
Association of Genetic Risk Factors for Psychiatric Disorders and Traits of These Disorders in a Swedish Population Twin Sample
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DOI：
10.1001/jamapsychiatry.2018.3652
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发表时间：
2019-03-01
期刊：
影响因子：
25.8
通讯作者：
Lichtenstein, Paul
中科院分区：
文献类型：
--
作者：
Taylor, Mark J.;Martin, Joanna;Lichtenstein, Paul
重要性与分类定义的精神疾病相关的精神病特征是可遗传的，并在普通人群中不同程度地存在。一般认为，诊断代表了人口中连续分布特征的极端，但这一假设尚未得到稳健的许多精神病phenotypes.Objective检验，以评估是否与精神疾病相关的遗传危险因素也与较温和的人口特征的连续变化。和参与者本研究结合了一种新的双胞胎分析方法与多基因风险评分（PRS）分析在一个大的人口为基础的双胞胎样本。表型和遗传数据来自瑞典儿童和青少年双胞胎研究。可获得1987年1月1日至2014年12月31日的住院患者数据和2001年1月1日至2013年12月31日的门诊患者数据。随访的最后一天是2014年12月31日。数据分析于2017年1月1日至2017年9月30日进行。主要结果和指标评估自闭症谱系障碍（ASD）、注意力缺陷/多动障碍（ADHD）、学习困难、抽动障碍（TDs）、强迫症（OCD）、焦虑、重度抑郁症（MDD）、躁狂、抑郁症、焦虑症、抑郁症、抑郁症、焦虑症、抑郁症、抑郁和精神病经历的研究对象是一对瑞典双胞胎。使用瑞典国家患者登记册确定临床精神病诊断的个人。联合分类/连续双胞胎模型被用来估计精神病诊断和连续性状之间的遗传相关性。基于独立发现遗传数据计算精神疾病的PRS。结果共获得13923对双生子的表型数据（35.1%异性和31.7%同性女性），9岁时，5165对15岁时为4273对（36.9%异性和34.0%同性女性），18岁时为4273对（36.5%异性和34.4%同性女性）。遗传数据可用于13412个人（50.2%女性）。许多精神病诊断和相应的性状之间的双胞胎遗传相关从0.31到0.69不等。抑郁性应激障碍与ASD的相关人群特征相关（9岁时β [SE] = 0.04 [0.01]），ADHD（9岁时β [SE] = 0.27 [0.03]），TD，（9岁时β [SE] = 0.02 [0.004]），强迫症（18岁时β [SE] = 0.13 [0.05]），焦虑（9岁时β [SE] = 0.18 [0.08]; 15岁时β [SE] = 0.07 [0.02]; 18岁时β [SE] = 0.40 [0]7]），MDD（9岁时β [SE] = 0.10 [0.03]; 15岁时[SE] = 0.11[0.02]; 18岁时β [SE] = 0.41[0]0]）和精神分裂症（18岁时β [SE] = 0.02 [0.01]）。多基因，iskscoesfordepressive症状与MDD诊断（优势比，1.16; 95%CI，1.02-1.32）。结论和相关性这些结果表明，与精神疾病相关的遗传因素也与整个一般人群的许多精神病表型的特征性状的温和变化。这项研究表明，许多精神疾病很可能是连续的表型，而不是目前在诊断手册中定义的分类实体，这对遗传研究有很强的影响。
IMPORTANCE Psychiatric traits associated with categorically defined psychiatric disorders are heritable and present to varying degrees in the general population. It is commonly assumed that diagnoses represent the extreme end of continuously distributed traits in the population, but this assumption has yet to be robustly tested for many psychiatric phenotypes.OBJECTIVE To assess whether genetic risk factors associated with psychiatric disorders are also associated with continuous variation in milder population traits.DESIGN, SETTING, AND PARTICIPANTS This study combined a novel twin analytic approach with polygenic risk score (PRS) analyses in a large population-based twin sample. Phenotypic and genetic data were available from the Child and Adolescent Twin Study in Sweden. Inpatient data were available for January 1, 1987, to December 31, 2014, and outpatient data for January 1, 2001, to December 31, 2013. The last day of follow-up was December 31, 2014. Data analysis was performed from January 1, 2017, to September 30, 2017.MAIN OUTCOMES AND MEASURES Questionnaires that assessed traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, tic disorders (TDs), obsessive-compulsive disorder (OCD), anxiety, major depressive disorder (MDD), mania, and psychotic experiences were administered to a large Swedish twin sample. Individuals with clinical psychiatric diagnoses were identified using the Swedish National Patient Register. Joint categorical/continuous twin modeling was used to estimate genetic correlations between psychiatric diagnoses and continuous traits. The PRSs for psychiatric disorders were calculated based on independent discovery genetic data. The association between PRSs for each disorder and associated continuous traits was tested.RESULTS Phenotype data were available for 13 923 twin pairs (35.1% opposite sex and 31.7% same-sex females) at 9 years of age, 5165 pairs (36.9% opposite sex and 34.0% same-sex females) at 15 years of age, and 4273 pairs (36.5% opposite sex and 34.4% same-sex females) at 18 years of age. Genetic data were available for 13 412 individuals (50.2% females). Twin genetic correlations between numerous psychiatric diagnoses and corresponding traits ranged from 0.31 to 0.69. Disorder PRSs were associated with related population traits for ASD (beta [SE] = 0.04 [0.01] at 9 years of age), ADHD (beta [SE] = 0.27 [0.03] at 9 years of age), TD, (beta [SE] = 0.02 [0.004] at 9 years of age), OCD (beta [SE] = 0.13 [0.05] at 18 years of age), anxiety (beta [SE] = 0.18 [0.08] at 9 years of age; beta [SE] = 0.07 [0.02] at 15 years of age; and beta [SE] = 0.40 [0]7] at 18 years of age), MDD (beta [SE] = 0.10 [0.03] at 9 years of age; [SE] = 0.11[0.02] at 15 years of age; and beta [SE] = 0.41[0]0] at 18 years of age), and schizophrenia (beta [SE] = 0.02 [0.01] at 18 years of age). Polygenic,iskscoesfordepres ive symptoms were associated with MDD diagnoses (odds ratio, 1.16; 95% CI, 1.02-1.32).CONCLUSION AND RELEVANCE These results suggest that genetic factors associated with psychiatric disorders are also associated with milder variation in characteristic traits throughout the general population for many psychiatric phenotypes. This study suggests that many psychiatric disorders are likely to be continuous phenotypes rather than the categorical entities currently defined in diagnostic manuals, which has strong implications for genetic research in particular.