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Molecular Autism
Published in: Molecular Autism 1/2011

Open Access 01-12-2011 | Research

Autism risk assessment in siblings of affected children using sex-specific genetic scores

Authors: Jerome Carayol, Gerard D Schellenberg, Beth Dombroski, Emmanuelle Genin, Francis Rousseau, Geraldine Dawson

Published in: Molecular Autism | Issue 1/2011

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Abstract

Background

The inheritance pattern in most cases of autism is complex. The risk of autism is increased in siblings of children with autism and previous studies have indicated that the level of risk can be further identified by the accumulation of multiple susceptibility single nucleotide polymorphisms (SNPs) allowing for the identification of a higher-risk subgroup among siblings. As a result of the sex difference in the prevalence of autism, we explored the potential for identifying sex-specific autism susceptibility SNPs in siblings of children with autism and the ability to develop a sex-specific risk assessment genetic scoring system.

Methods

SNPs were chosen from genes known to be associated with autism. These markers were evaluated using an exploratory sample of 480 families from the Autism Genetic Resource Exchange (AGRE) repository. A reproducibility index (RI) was proposed and calculated in all children with autism and in males and females separately. Differing genetic scoring models were then constructed to develop a sex-specific genetic score model designed to identify individuals with a higher risk of autism. The ability of the genetic scores to identify high-risk children was then evaluated and replicated in an independent sample of 351 affected and 90 unaffected siblings from families with at least 1 child with autism.

Results

We identified three risk SNPs that had a high RI in males, two SNPs with a high RI in females, and three SNPs with a high RI in both sexes. Using these results, genetic scoring models for males and females were developed which demonstrated a significant association with autism (P = 2.2 × 10-6 and 1.9 × 10-5, respectively).

Conclusions

Our results demonstrate that individual susceptibility associated SNPs for autism may have important differential sex effects. We also show that a sex-specific risk score based on the presence of multiple susceptibility associated SNPs allow for the identification of subgroups of siblings of children with autism who have a significantly higher risk of autism.
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Metadata
Title
Autism risk assessment in siblings of affected children using sex-specific genetic scores
Authors
Jerome Carayol
Gerard D Schellenberg
Beth Dombroski
Emmanuelle Genin
Francis Rousseau
Geraldine Dawson
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2011
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/2040-2392-2-17

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