Common genetic risk factors in ASD and ADHD co-occurring families.
Common genetic risk factors in ASD and ADHD co-occurring families.
复制标题
DOI：
10.1007/s00439-022-02496-z
复制
发表时间：
2023-02
期刊：
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD）是两种常见的神经发育障碍。然而，其共同发生的遗传机制仍不清楚。新泽西语言和自闭症遗传学研究（NJLAGS）收集了100多个家庭，其中至少有一个成员受到ASD的影响。NJLAGS家族表现出ADHD的高患病率，并提供了一个很好的机会来研究ASD和ADHD的共同遗传风险因素。NJLAGS家族的连锁研究揭示了12号和17号染色体上与ADHD显著相关的区域。利用来自73个NJLAGS家族的272个样本的全基因组测序数据，我们确定了ASD和ADHD的潜在风险基因。在连锁区域内，我们使用基于谱系的基因优先排序方法确定了36个与ADHD相关的基因。KDM 6 B（赖氨酸脱甲基酶6 B）是排名最高的基因，这是一个已知的神经发育障碍的风险基因，包括ASD和ADHD。在全基因组水平上，我们从小变异和结构变异的分析中确定了207个候选基因，包括已知和新基因。使用富集和蛋白质-蛋白质相互作用网络分析，我们确定了ASD和ADHD候选基因的基因本体论术语和途径，如纤毛功能和阳离子通道活性。在我们的研究中确定的候选基因和途径提高了对ASD和ADHD遗传病因的理解，并将在未来为ASD和ADHD带来新的诊断或治疗干预。
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two major neurodevelopmental disorders that frequently co-occur. However, the genetic mechanism of the co-occurrence remains unclear. The New Jersey Language and Autism Genetics Study (NJLAGS) collected more than 100 families with at least one member affected by ASD. NJLAGS families show a high prevalence of ADHD and provide a good opportunity to study shared genetic risk factors for ASD and ADHD. The linkage study of the NJLAGS families revealed regions on chromosomes 12 and 17 that are significantly associated with ADHD. Using whole-genome sequencing data on 272 samples from 73 NJLAGS families, we identified potential risk genes for ASD and ADHD. Within the linkage regions, we identified 36 genes that are associated with ADHD using a pedigree-based gene prioritization approach. KDM6B (Lysine Demethylase 6B) is the highest-ranking gene, which is a known risk gene for neurodevelopmental disorders, including ASD and ADHD. At the whole-genome level, we identified 207 candidate genes from the analysis of both small variants and structure variants, including both known and novel genes. Using enrichment and protein–protein interaction network analyses, we identified gene ontology terms and pathways enriched for ASD and ADHD candidate genes, such as cilia function and cation channel activity. Candidate genes and pathways identified in our study improve the understanding of the genetic etiology of ASD and ADHD and will lead to new diagnostic or therapeutic interventions for ASD and ADHD in the future.
登录
查看更多内容
影响因子：
12.3
作者：
Doherty JL;Owen MJ
通讯作者：
Owen MJ
影响因子：
1.8
作者：
Govil, M.;Vieland, V. J.
通讯作者：
Vieland, V. J.
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
2.1
作者：
Hu, Hao;Huff, Chad D.;Moore, Barry;Flygare, Steven;Reese, Martin G.;Yandell, Mark
通讯作者：
Yandell, Mark
影响因子：
64.8
作者：
Dickinson ME;Flenniken AM;Ji X;Teboul L;Wong MD;White JK;Meehan TF;Weninger WJ;Westerberg H;Adissu H;Baker CN;Bower L;Brown JM;Caddle LB;Chiani F;Clary D;Cleak J;Daly MJ;Denegre JM;Doe B;Dolan ME;Edie SM;Fuchs H;Gailus-Durner V;Galli A;Gambadoro A;Gallegos J;Guo S;Horner NR;Hsu CW;Johnson SJ;Kalaga S;Keith LC;Lanoue L;Lawson TN;Lek M;Mark M;Marschall S;Mason J;McElwee ML;Newbigging S;Nutter LM;Peterson KA;Ramirez-Solis R;Rowland DJ;Ryder E;Samocha KE;Seavitt JR;Selloum M;Szoke-Kovacs Z;Tamura M;Trainor AG;Tudose I;Wakana S;Warren J;Wendling O;West DB;Wong L;Yoshiki A;International Mouse Phenotyping Consortium;Jackson Laboratory;Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS);Charles River Laboratories;MRC Harwell;Toronto Centre for Phenogenomics;Wellcome Trust Sanger Institute;RIKEN BioResource Center;MacArthur DG;Tocchini-Valentini GP;Gao X;Flicek P;Bradley A;Skarnes WC;Justice MJ;Parkinson HE;Moore M;Wells S;Braun RE;Svenson KL;de Angelis MH;Herault Y;Mohun T;Mallon AM;Henkelman RM;Brown SD;Adams DJ;Lloyd KC;McKerlie C;Beaudet AL;Bućan M;Murray SA
通讯作者：
Murray SA