Research
Assessing the impact of a combined analysis of four common low-risk genetic variants on autism risk
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* Corresponding author: Jerome Carayol jerome.carayol@integragen.com
1 IntegraGen SA, Evry, France
2 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
3 Department of Human Genetics, CEA-Genomics Institute, Evry, France
4 Institute of Medical Biometry and Statistics, University of Luebeck, Luebeck, Germany
5 Autism Speaks and the Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Molecular Autism 2010, 1:4 doi:10.1186/2040-2392-1-4
Published: 22 February 2010Abstract
Background
Autism is a complex disorder characterized by deficits involving communication, social interaction, and repetitive and restrictive patterns of behavior. Twin studies have shown that autism is strongly heritable, suggesting a strong genetic component. In other disease states with a complex etiology, such as type 2 diabetes, cancer and cardiovascular disease, combined analysis of multiple genetic variants in a genetic score has helped to identify individuals at high risk of disease. Genetic scores are designed to test for association of genetic markers with disease.
Method
The accumulation of multiple risk alleles markedly increases the risk of being affected, and compared with studying polymorphisms individually, it improves the identification of subgroups of individuals at greater risk. In the present study, we show that this approach can be applied to autism by specifically looking at a high-risk population of children who have siblings with autism. A two-sample study design and the generation of a genetic score using multiple independent genes were used to assess the risk of autism in a high-risk population.
Results
In both samples, odds ratios (ORs) increased significantly as a function of the number of risk alleles, with a genetic score of 8 being associated with an OR of 5.54 (95% confidence interval [CI] 2.45 to 12.49). The sensitivities and specificities for each genetic score were similar in both analyses, and the resultant area under the receiver operating characteristic curves were identical (0.59).
Conclusions
These results suggest that the accumulation of multiple risk alleles in a genetic score is a useful strategy for assessing the risk of autism in siblings of affected individuals, and may be better than studying single polymorphisms for identifying subgroups of individuals with significantly greater risk.