| Literature DB >> 34050743 |
Katherine E Lawrence1, Leanna M Hernandez1, Emily Fuster1, Namita T Padgaonkar1, Genevieve Patterson1, Jiwon Jung1, Nana J Okada1, Jennifer K Lowe2, Jackson N Hoekstra2, Allison Jack3, Elizabeth Aylward4, Nadine Gaab5, John D Van Horn6, Raphael A Bernier7, James C McPartland8, Sara J Webb7,9, Kevin A Pelphrey10, Shulamite A Green1, Susan Y Bookheimer1, Daniel H Geschwind2,11, Mirella Dapretto1.
Abstract
The biological mechanisms underlying the greater prevalence of autism spectrum disorder in males than females remain poorly understood. One hypothesis posits that this female protective effect arises from genetic load for autism spectrum disorder differentially impacting male and female brains. To test this hypothesis, we investigated the impact of cumulative genetic risk for autism spectrum disorder on functional brain connectivity in a balanced sample of boys and girls with autism spectrum disorder and typically developing boys and girls (127 youth, ages 8-17). Brain connectivity analyses focused on the salience network, a core intrinsic functional connectivity network which has previously been implicated in autism spectrum disorder. The effects of polygenic risk on salience network functional connectivity were significantly modulated by participant sex, with genetic load for autism spectrum disorder influencing functional connectivity in boys with and without autism spectrum disorder but not girls. These findings support the hypothesis that autism spectrum disorder risk genes interact with sex differential processes, thereby contributing to the male bias in autism prevalence and proposing an underlying neurobiological mechanism for the female protective effect.Entities:
Keywords: autism spectrum disorder; female protective effect; functional connectivity; imaging genetics; polygenic risk
Mesh：
Year: 2022 PMID： 34050743 PMCID： PMC8967090 DOI： 10.1093/brain/awab204
Source DB: PubMed Journal: Brain ISSN： 0006-8950 Impact factor: 15.255