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Investigation of gene–environment interactions in relation to tic severity
Journal of Neural Transmission ( IF 3.2 ) Pub Date : 2021-08-13 , DOI: 10.1007/s00702-021-02396-y
Mohamed Abdulkadir 1, 2 , Dongmei Yu 3, 4 , Lisa Osiecki 4 , Robert A King 5 , Thomas V Fernandez 5 , Lawrence W Brown 6 , Keun-Ah Cheon 7 , Barbara J Coffey 8, 9, 10 , Blanca Garcia-Delgar 11 , Donald L Gilbert 12 , Dorothy E Grice 8 , Julie Hagstrøm 13 , Tammy Hedderly 14 , Isobel Heyman 15 , Hyun Ju Hong 16 , Chaim Huyser 17 , Laura Ibanez-Gomez 18 , Young Key Kim 19 , Young-Shin Kim 20 , Yun-Joo Koh 21 , Sodahm Kook 22 , Samuel Kuperman 23 , Bennett Leventhal 20 , Marcos Madruga-Garrido 24 , Athanasios Maras 25 , Pablo Mir 26 , Astrid Morer 27 , Alexander Münchau 28 , Kerstin J Plessen 13 , Veit Roessner 29 , Eun-Young Shin 7 , Dong-Ho Song 30 , Jungeun Song 31 , Frank Visscher 32 , Samuel H Zinner 33 , Carol A Mathews 34 , Jeremiah M Scharf 3, 4 , Jay A Tischfield 2 , Gary A Heiman 2 , Andrea Dietrich 1 , Pieter J Hoekstra 1
Affiliation  

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.



中文翻译:


与抽动严重程度相关的基因-环境相互作用的调查



抽动秽语综合症(TS)是一种与遗传和环境因素有关的神经精神疾病。我们采用纯病例 ( N = 518) 设计,研究了先前与抽动秽语综合征和相关疾病相关的基因位点,这些基因位点与产前和围产期逆境的相互作用以及抽动严重程度的相关性。我们评估了 98 个单核苷酸多态性 (SNP),这些单核苷酸多态性 (SNP) 选自 (I) TS 全基因组关联研究 (GWAS) 中的顶级 SNP; (II) 强迫症 (OCD)、注意力缺陷/多动障碍 (ADHD) 和自闭症谱系障碍 (ASD) 的 GWAS 中的主要 SNP; (III) 先前参与 TS 候选基因研究的 SNP; (IV) 先前与 OCD 或 ASD 有关的 SNP; (V) 标记神经递质相关候选基因中的 S​​NP。使用线性回归模型来检查 SNP 对抽动严重程度的主要影响,以及这些 SNP 与累积的产前和围产期逆境评分的相互作用。寻求重复样本中满足显着性阈值(校正多次测试后)的 SNP ( N = 678)。先前在 TS 荟萃分析中涉及的一个 SNP (rs7123010) 与较高的抽动严重程度显着相关。我们发现了另一个顶级 TS GWAS SNP rs6539267 的基因-环境相互作用。这些发现没有被独立重复。我们的研究强调了 TS GWAS 在基因-环境研究中的未来潜力。

更新日期:2021-08-19
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