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Molecular Autism
Published in: Molecular Autism 1/2015

Open Access 01-12-2015 | Research

The female protective effect in autism spectrum disorder is not mediated by a single genetic locus

Authors: Jake Gockley, A Jeremy Willsey, Shan Dong, Joseph D Dougherty, John N Constantino, Stephan J Sanders

Published in: Molecular Autism | Issue 1/2015

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Abstract

Background

A 4:1 male to female sex bias has consistently been observed in autism spectrum disorder (ASD). Epidemiological and genetic studies suggest a female protective effect (FPE) may account for part of this bias; however, the mechanism of such protection is unknown. Quantitative assessment of ASD symptoms using the Social Responsiveness Scale (SRS) shows a bimodal distribution unique to females in multiplex families. This leads to the hypothesis that a single, common genetic locus on chromosome X might mediate the FPE and produce the ASD sex bias. Such a locus would represent a major therapeutic target and is likely to have been missed by conventional genome-wide association study (GWAS) analysis.

Methods

To explore this possibility, we performed an association study in affected versus unaffected females, considering three tiers of single nucleotide polymorphisms (SNPs) as follows: 1) regions of chromosome X that escape X-inactivation, 2) all of chromosome X, and 3) genome-wide.

Results

No evidence of a SNP meeting the criteria for a single FPE locus was observed, despite the analysis being well powered to detect this effect.

Conclusions

The results do not support the hypothesis that the FPE is mediated by a single genetic locus; however, this does not exclude the possibility of multiple genetic loci playing a role in the FPE.
Appendix
Available only for authorised users
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Metadata
Title
The female protective effect in autism spectrum disorder is not mediated by a single genetic locus
Authors
Jake Gockley
A Jeremy Willsey
Shan Dong
Joseph D Dougherty
John N Constantino
Stephan J Sanders
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2015
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-015-0014-3

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