Pleiotropic Mechanisms Indicated for Sex Differences in Autism.

Title	Pleiotropic Mechanisms Indicated for Sex Differences in Autism.
Publication Type	Journal Article
Year of Publication	2016
Authors	Mitra I, Tsang K, Ladd-Acosta C, Croen LA, Aldinger KA, Hendren RL, Traglia M, Lavillaureix A, Zaitlen N, Oldham MC, Levitt P, Nelson S, Amaral DG, Hertz-Picciotto I, M Fallin D, Weiss LA
Journal	PLoS genetics
Volume	12
Pagination	e1006425
Date Published	11
ISSN	1553-7404
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.
DOI	10.1371/journal.pgen.1006425