Elevated Polygenic Burden for Autism Spectrum Disorder Is Associated With the Broad Autism Phenotype in Mothers of Individuals With Autism Spectrum Disorder

Biol Psychiatry. 2021 Mar 1;89(5):476-485. doi: 10.1016/j.biopsych.2020.08.029. Epub 2020 Sep 12.


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Autism spectrum disorder; Broad autism phenotype; Common genetic variation; Endophenotype; Polygenic scores; Pragmatic language.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autism Spectrum Disorder* / genetics
  • Autistic Disorder*
  • Child
  • Fathers
  • Female
  • Humans
  • Male
  • Mothers
  • Phenotype