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Author Spotlight: Exploring Autism Spectrum Disorder Symptoms in Fruit Flies — Genetic Models and Behavioral Tests
Published on: September 6, 2024
Pleiotropic Mechanisms Indicated for Sex Differences in Autism
Ileena Mitra1, Kathryn Tsang1, Christine Ladd-Acosta2
1Department of Psychiatry and Institute for Human Genetics, University of California, San Francisco, California, United States of America.
Abstract:
Sexual dimorphism in common disease is pervasive, including a dramatic male preponderance in autism spectrum disorders (ASDs). Potential genetic explanations include a liability threshold model requiring increased polymorphism risk in females, sex-limited X-chromosome contribution, gene-environment interaction driven by differences in hormonal milieu, risk influenced by genes sex-differentially expressed in early brain development, or contribution from general mechanisms of sexual dimorphism shared with secondary sex characteristics. Utilizing a large single nucleotide polymorphism (SNP) dataset, we identify distinct sex-specific genome-wide significant loci. We investigate genetic hypotheses and find no evidence for increased genetic risk load in females, but evidence for sex heterogeneity on the X chromosome, and contribution of sex-heterogeneous SNPs for anthropometric traits to ASD risk. Thus, our results support pleiotropy between secondary sex characteristic determination and ASDs, providing a biological basis for sex differences in ASDs and implicating non brain-limited mechanisms.
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