Pedersen Julie Holst, Skytthe Axel, Bybjerg-Grauholm Jonas, Kucukyildiz Asli Sena, Skov Liselotte, Debes Nanette Mol, Tümer Zeynep
Department of Pediatrics, Copenhagen University Hospital, Herlev, Denmark.
The Danish Twin Registry, Epidemiology, Biostatistics, and Biodemography, Institute of Public Health, University of Southern, Denmark.
J Psychiatr Res. 2022 Feb;146:297-303. doi: 10.1016/j.jpsychires.2021.11.019. Epub 2021 Nov 9.
Gilles de la Tourette Syndrome (GTS) is a multifactorial neurodevelopmental disorder characterized by tics and multiple comorbidities. The pathophysiology is not yet fully understood, but both environmental and genetic risk factors seem to be involved. Twin studies provide important knowledge on genetic factors. We assessed the concordance of GTS and chronic tic disorders (CTD) in monozygotic (MZ) twins, and examined tic severity, symptoms of obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder and autism spectrum disorder. Twin pairs, where at least one twin was diagnosed with any tic disorder, were identified through Danish Twin Registry, Psychiatric Central Registry, Danish National Patient Registry and National Tourette Clinic, Copenhagen University Hospital, Herlev. Zygosity was tested with single-nucleotide polymorphism (SNP) genotyping and clinical assessment was done with validated tools. 14 MZ twin pairs were included: five were discordant. Seven twin pairs were concordant for GTS, and for two pairs one twin had GTS and the other CTD. Among the twins with CTD or GTS, 50% had at least one comorbidity, which is higher than in background populations. The GTS + OCD-phenotype was significantly more frequent among GTS-concordant than among discordant twins. No statistically significant differences were found between the GTS-concordant and discordant twin pairs regarding tic severity or comorbidities. Thorough clinical assessment and SNP-based genotyping are important when conducting clinical twin studies. We found high concordance of GTS and CTD, which supports the notion that both disorders have common genetic risk factors. Further studies with larger cohorts including dizygotic twins are warranted for more conclusive results.
抽动秽语综合征(GTS)是一种多因素神经发育障碍,其特征为抽动和多种共病。其病理生理学尚未完全明确,但环境和遗传风险因素似乎都有涉及。双胞胎研究为遗传因素提供了重要知识。我们评估了同卵双胞胎(MZ)中GTS和慢性抽动障碍(CTD)的一致性,并检查了抽动严重程度、强迫症(OCD)症状、注意力缺陷多动障碍和自闭症谱系障碍。通过丹麦双胞胎登记处、精神病学中央登记处、丹麦国家患者登记处和哥本哈根大学医院赫勒夫国家抽动秽语综合征诊所,识别出至少有一名双胞胎被诊断患有任何抽动障碍的双胞胎对。通过单核苷酸多态性(SNP)基因分型检测合子性,并用经过验证的工具进行临床评估。纳入了14对MZ双胞胎对:5对不一致。7对双胞胎对GTS一致,2对中一对双胞胎患有GTS,另一对患有CTD。在患有CTD或GTS的双胞胎中,50%至少有一种共病,这高于背景人群。GTS + OCD表型在GTS一致的双胞胎中比在不一致的双胞胎中明显更常见。在GTS一致和不一致的双胞胎对之间,在抽动严重程度或共病方面未发现统计学上的显著差异。进行临床双胞胎研究时,全面的临床评估和基于SNP的基因分型很重要。我们发现GTS和CTD有高度一致性,这支持了这两种疾病有共同遗传风险因素的观点。需要对包括异卵双胞胎在内的更大队列进行进一步研究以获得更确凿的结果。