Department of Genetics, Rutgers, the State University of New Jersey, and the Human Genetics Institute of New Jersey, Piscataway, New Jersey; Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Psychiatry, Center for OCD, Anxiety and Related Disorders, and Genetics Institute, University of Florida College of Medicine, Gainesville, Florida.
Biol Psychiatry. 2019 Feb 15;85(4):298-304. doi: 10.1016/j.biopsych.2018.09.011. Epub 2018 Sep 29.
Tourette syndrome (TS) has a well-established genetic background, but its genetic architecture remains largely unknown. The authors investigated the role of polygenic risk scores (PRSs) derived from a TS genome-wide association study in relation to the occurrence of tics and associated traits in a general population cohort.
Using the most recent TS genome-wide association study (n = 4819 cases; n = 9488 controls) as the discovery sample, PRSs were calculated in Avon Longitudinal Study of Parents and Children participants (n = 8941). Regression analyses were used to assess whether PRS predicted the presence and chronicity of tics, and symptom severity of obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and autism spectrum disorder in Avon Longitudinal Study of Parents and Children participants.
Following correction for multiple testing, the PRS significantly predicted the presence (R = .48%, p empirical = .01, Q = .04) but not the chronicity (R = .16%, p empirical = .07, Q = .14) of tics in the Avon Longitudinal Study of Parents and Children cohort; it did not predict the severity of obsessive-compulsive disorder (R = .11%, p empirical = .11, Q = .15), attention-deficit/hyperactivity disorder (R = .09%, p empirical = .19, Q = .21), or autism spectrum disorder (R = .12%, p empirical = .09, Q = .14).
The authors found a significant polygenic component of tics occurring in a general population cohort based on PRS derived from a genome-wide association study of individuals with a TS diagnosis. This finding supports the notion that tics along a spectrum from nonclinical to clinical symptom levels share a similar genetic background.
妥瑞氏综合征（TS）具有明确的遗传背景，但遗传结构仍很大程度上未知。作者研究了源自 TS 全基因组关联研究的多基因风险评分（PRSs）与一般人群队列中抽动症和相关特征发生的关系。
使用最新的 TS 全基因组关联研究（n=4819 例病例；n=9488 例对照）作为发现样本，在阿冯纵向父母和儿童参与者（n=8941）中计算 PRS。回归分析用于评估 PRS 是否预测阿冯纵向父母和儿童参与者中抽动的存在和慢性、强迫症、注意缺陷/多动障碍和自闭症谱系障碍的症状严重程度。
经多重检验校正后，PRS 显著预测了阿冯纵向父母和儿童队列中抽动的存在（R=.48%，p 经验 =.01，Q=.04），但不能预测其慢性（R=.16%，p 经验 =.07，Q=.14）；它不能预测强迫症（R=.11%，p 经验 =.11，Q=.15）、注意缺陷/多动障碍（R=.09%，p 经验 =.19，Q=.21）或自闭症谱系障碍（R=.12%，p 经验 =.09，Q=.14）的严重程度。
作者基于源自 TS 诊断个体的全基因组关联研究的 PRS，发现了一般人群队列中抽动发生的显著多基因成分。这一发现支持了这样一种观点，即在从非临床到临床症状水平的谱系上，抽动症具有相似的遗传背景。
