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研究鉴定出自闭症谱系障碍、注意力缺陷多动障碍和病例亚群的共同和差异化的遗传结构
2022-09-30 23:14

丹麦奥尔胡斯大学Anders D. Børglum、Manuel Mattheisen等研究人员合作鉴定出自闭症谱系障碍、注意力缺陷多动障碍和病例亚群的共同和差异化的遗传结构。2022年9月26日,国际知名学术期刊《自然—遗传学》在线发表了这一成果。

注意力缺陷多动症(ADHD)和自闭症谱系障碍(ASD)是高度可遗传的神经发育疾病,其遗传病因有很大的重叠。研究人员通过对大型数据集的跨疾病分析,剖析了它们共同的和不同的遗传病理学。研究人员确定了这些疾病共有的7个位点和5个区分它们的位点。所有五个差异化的基因座在两种疾病中显示出相反的等位基因方向,并与其他性状有明显的关联,包括教育程度、神经质和区域脑容量。与大脑转录组数据的整合使研究人员能够鉴别并优先考虑几个明显相关的基因。导致这两种疾病的共同基因组部分与其他精神病表型密切相关,而差异化的部分与认知特征的相关性最强。
 
其他分析显示,被诊断为ASD和ADHD的个体具有两种疾病的双重遗传倾向,并且与仅有ASD和仅有ADHD的亚组相比,显示出与其他性状不同的遗传关联模式。这些结果提供了对一种或两种病症发展的生物学基础的见解,以及对驱动心理病理学向ADHD或ASD发展的歧视性因素的见解。
 
附:英文原文

Title: Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups

Author: Mattheisen, Manuel, Grove, Jakob, Als, Thomas D., Martin, Joanna, Voloudakis, Georgios, Meier, Sandra, Demontis, Ditte, Bendl, Jaroslav, Walters, Raymond, Carey, Caitlin E., Rosengren, Anders, Strom, Nora I., Hauberg, Mads Engel, Zeng, Biao, Hoffman, Gabriel, Zhang, Wen, Bybjerg-Grauholm, Jonas, Bkvad-Hansen, Marie, Agerbo, Esben, Cormand, Bru, Nordentoft, Merete, Werge, Thomas, Mors, Ole, Hougaard, David M., Buxbaum, Joseph D., Faraone, Stephen V., Franke, Barbara, Dalsgaard, Sren, Mortensen, Preben B., Robinson, Elise B., Roussos, Panos, Neale, Benjamin M., Daly, Mark J., Brglum, Anders D.

Issue&Volume: 2022-09-26

Abstract: Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.

DOI: 10.1038/s41588-022-01171-3

Source: https://www.nature.com/articles/s41588-022-01171-3

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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