Pleiotropic Mechanisms Indicated for Sex Differences in Autism.
PLoS Genet
; 12(11): e1006425, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27846226
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transtornos Globais do Desenvolvimento Infantil
/
Cromossomos Humanos X
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Transtorno do Espectro Autista
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article