Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University, Evanston, Illinois.
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
Biol Psychiatry. 2021 Mar 1;89(5):476-485. doi: 10.1016/j.biopsych.2020.08.029. Epub 2020 Sep 12.
Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder that encompasses a complex and heterogeneous set of traits. Subclinical traits that mirror the core features of ASD, referred to as the broad autism phenotype (BAP), have been documented repeatedly in unaffected relatives and are believed to reflect underlying genetic liability to ASD. The BAP may help inform the etiology of ASD by allowing the stratification of families into more phenotypically and etiologically homogeneous subgroups. This study explores polygenic scores related to the BAP.
Phenotypic and genotypic information were obtained from 2614 trios from the Simons Simplex Collection. Polygenic scores of ASD (ASD-PGSs) were generated across the sample to determine the shared genetic overlap between the BAP and ASD. Maternal and paternal ASD-PGSs were explored in relation to BAP traits and their child's ASD symptomatology.
Maternal pragmatic language was related to child's social communicative atypicalities. In fathers, rigid personality was related to increased repetitive behaviors in children. Maternal (but not paternal) ASD-PGSs were related to the pragmatic language and rigid BAP domains.
Associations emerged between parent and child phenotypes, with more associations emerging in mothers than in fathers. ASD-PGS associations emerged with BAP in mothers only, highlighting the potential for a female protective factor, and implicating the polygenic etiology of ASD-related phenotypes in the BAP.
自闭症谱系障碍（ASD）是一种多因素神经发育障碍，包含一系列复杂且异质的特征。在未受影响的亲属中，反复记录到与 ASD 核心特征相似的亚临床特征，称为广泛自闭症表型（BAP），被认为反映了 ASD 的潜在遗传易感性。BAP 可以通过将家庭分层为表型和病因学上更同质的亚组，为 ASD 的病因提供信息。本研究探讨了与 BAP 相关的多基因评分。
从西蒙斯单纯性集合的 2614 个三亲家庭中获得了表型和基因型信息。在整个样本中生成了 ASD 的多基因评分（ASD-PGSs），以确定 BAP 和 ASD 之间的共同遗传重叠。探索了母亲和父亲的 ASD-PGSs 与 BAP 特征及其孩子的 ASD 症状之间的关系。
母亲的语用语言与孩子的社交沟通异常有关。在父亲中，僵化的个性与孩子的重复行为增加有关。母亲（而不是父亲）的 ASD-PGSs 与语用和僵化的 BAP 领域有关。
在父母和孩子的表型之间出现了关联，母亲比父亲出现了更多的关联。ASD-PGS 与 BAP 之间仅在母亲中出现关联，突出了女性保护因素的潜力，并暗示了 ASD 相关表型的多基因病因与 BAP 有关。
