AMBRA1, Autophagy, and the Extreme Male Brain Theory of Autism. (10th October 2019)

• Record Type: Journal Article
• Authors: Crespi, Bernard; Read, Silven; Ly, Amy; Hurd, Peter
• Other Names: Canitano Roberto Academic Editor.
• Is Part Of: Autism research and treatment. Volume 2019(2019)
• Publication Date: 2019-10-10
• Subjects: Autism -- Periodicals; Autism -- Research -- Periodicals; Autism -- Treatment -- Periodicals; Autistic people -- Services for -- Periodicals; 616.85882005
• DOI: 10.1155/2019/1968580
• Languages: English
• ISSNs: 2090-1925

Abstract

Abstract : The extreme male brain theory of autism posits that its male bias is mediated by exaggeration of male-biased sex differences in the expression of autism-associated traits found in typical populations. The theory is supported by extensive phenotypic evidence, but no genes have yet been described with properties that fit its predictions. The autophagy-associated gene AMBRA1 represents one of the top genome-wide "hits" in recent GWAS studies of schizophrenia, shows sex-differential expression, and has been linked with autism risk and traits in humans and mice, especially or exclusively among females. We genotyped the AMBRA1 autism-risk SNP in a population of typical humans who were scored for the dimensional expression of autistic and schizotypal traits. Females, but not males, homozygous for the GG genotype showed a significant increase in score for the single trait, the Autism Quotient-Imagination subscale, that exhibits a strong, significant male bias in typical populations. As such, females with this genotype resembled males for this highly sexually dimorphic, autism-associated phenotype. These findings support the extreme male brain hypothesis and indicate that sex-specific genetic effects can mediate aspects of risk for autism.