• Role of Genetics in Autism
• Common Variants in Autism
• What is the ARISk Test?
• How to order the ARISk Test
• Clinical Summary
• How to Collect DNA Sample
• ARISk Test Development
• Understanding the Report
• Results from Parental Survey
• Contact a Genetic Counselor
• Publications

Developing the ARISk Test

Identifying new biomarkers for autism prediction

• High heritability (70-90%) but rare variants (CNVs, mutations…) explain only10%-20% of autism cases. 
• Common variants with modest associated risk have been linked to autism¹ and their accumulation significantly increases autism risk.^2,3

• Several genome-wide association studies (GWAS) have been performed but with limited success ^4-6 because of heterogeneity of autism and small sample size.

Extracting weak signals from noise in GWAS

• Newer research methods have been identified which enable the ability to identify common variants with weak statistical signals from GWASs performed for complex neuropsychiatric diseases and prioritize genes to identify those associated with the disorder.^7,8
  
• IntegraGen used these newer discovery methods to combine biological knowledge associated with gene function with statistical data to identify common variants associated with autism.

GWAS studies

• IntegraGen conducted GWASs utilizing DNA samples from multiplex families (families with more than one child with autism).
• Study population used for GWASs included nearly 1,000 children with autism and over 300 unaffected siblings
• 4 separate GWAS studies performed; affected males, affected females, affected males and females combined and unaffected siblings

SNP selection

• SNPs identified via GWASs were then scored based on functional biological characteristics for their associated genes.
• SNPs achieving a threshold score where then studied in two different independent multiplex family populations determine replicability and reproduciblity of the SNP's association with autism.
• Multiplex family populations used for studies included 1,200 families representing nearly 2,000 children with autism and approximately 600 unaffected siblings.
• SNPs with poor replication and reproducibility were excluded as non-informative for risk assessment purpose
• Replicability and reproducibility of deleterious alleles were calculated for males and females separately.
• SNPs identified were combined with 8 SNPs from previously published research conducted by IntegraGen.²
   

Click here to see detailed information for the SNPs included in the ARISk^® Test.

Click here to view a technical report describing the development and results associated with the ARISk^® Test.

References

1. Abrahams & Geschwind. Nat Rev Genet, 2008
2. Carayol , et al.  Molecular Autism, 2011
3. Carayol , et al.  Molecular Autism, 2011
4. Wang K, et al. Nature, 2009
5. Anney R, et al. Human Molecular Genetics, 2010
6. Weiss LA, et al. Nature, 2009
7. Patel et al. Am J Hum Genet, 2010
8. O’Dushlaine et al. Mol Psychiatry, 2010