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研究揭示自闭症表型异质性的遗传相关性
作者:小柯机器人 发布时间:2022/6/5 10:09:55

英国剑桥大学Simon Baron-Cohen、Varun Warrier等研究人员合作揭示自闭症表型异质性的遗传相关性。该项研究成果于2022年6月2日在线发表在《自然—遗传学》杂志上。

研究人员表示,自闭症的大量表型异质性限制了人们对其遗传病学的理解。
 
为了解决这个问题,研究人员调查了自闭症患者(最多12,893人)在自闭症的核心特征和相关特征、同时发生的发育障碍和性别方面的遗传差异。研究人员对自闭症患者的核心特征进行了全面的因子分析,确定了六个因子。常见的遗传变异与核心因素有关,但新的变异则没有。结果发现,较高的自闭症多基因评分(PGS)与自闭症患者共患发育障碍的可能性较低有关。此外,在没有并发智力障碍(ID)的自闭症患者中,与男性相比,自闭症PGS由自闭症女性过度继承。
 
最后,研究人员观察到自闭症男性和无ID的自闭症患者的SNP遗传性更高。更深入的表型特征将对确定复杂的基础遗传学如何塑造自闭症的认知、行为和共患情况至关重要。
 
附:英文原文

Title: Genetic correlates of phenotypic heterogeneity in autism

Author: Warrier, Varun, Zhang, Xinhe, Reed, Patrick, Havdahl, Alexandra, Moore, Tyler M., Cliquet, Freddy, Leblond, Claire S., Rolland, Thomas, Rosengren, Anders, Rowitch, David H., Hurles, Matthew E., Geschwind, Daniel H., Brglum, Anders D., Robinson, Elise B., Grove, Jakob, Martin, Hilary C., Bourgeron, Thomas, Baron-Cohen, Simon

Issue&Volume: 2022-06-02

Abstract: The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (nmax=12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.

DOI: 10.1038/s41588-022-01072-5

Source: https://www.nature.com/articles/s41588-022-01072-5

期刊信息

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:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex