Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes
Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes
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DOI：
10.1038/mp.2010.75
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发表时间：
2010-09-14
影响因子：
11
通讯作者：
White, P. S.
中科院分区：
文献类型：
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作者：
Elia, J.;Gai, X.;Xie, H. M.;Perin, J. C.;Geiger, E.;Glessner, J. T.;D'arcy, M.;deBerardinis, R.;Frackelton, E.;Kim, C.;Lantieri, F.;Muganga, B. M.;Wang, L.;Takeda, T.;Rappaport, E. F.;Grant, S. F. A.;Berrettini, W.;Devoto, M.;Shaikh, T. H.;Hakonarson, H.;White, P. S.
注意力缺陷多动障碍（ADHD）是一种常见的高度遗传性疾病，但潜在风险的特定遗传因素仍然难以捉摸。为了评估结构变异在ADHD中的作用，我们在335名ADHD患者及其父母中发现了222种遗传拷贝数变异（CNVs），这些变异在2026名无关的健康个体中未检测到。虽然在ADHD队列中相对于对照组没有发现过量的CNV，无论是缺失还是重复，但在自闭症，精神分裂症和Tourette综合征研究中报告为候选基因的遗传罕见CNV相关基因集显着富集，包括A2BP 1，AUTS 2，CNTNAP 2和IMMP 2L。ADHD CNV基因集也显著富集了已知对心理和神经功能重要的基因，包括学习，行为，突触传递和中枢神经系统发育。四个独立的缺失位于蛋白酪氨酸磷酸酶基因PTPRD内，PTPRD最近被认为是不宁腿综合征的候选基因，该综合征经常与ADHD一起出现。在受影响的父母和所有三个受影响的后代中发现了谷氨酸受体基因GRM5的缺失，这些后代的ADHD表型与GRM5缺失小鼠的表型非常相似。总之，这些结果表明，罕见的遗传结构变异在ADHD的发展中起着重要的作用，并指出了一组假定的候选基因，以进一步研究ADHD的病因。
Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD.
影响因子：
11
作者：
通讯作者：
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