Project Detail
Interagency Autism Coordinating Committee (IACC) logo
Office of Autism Research Coordination (OARC) logo

Dissecting epistasis and pleiotropy in autism towards personalized medicine  

Genome-wide association studies have indicated that main effects of common polymorphisms or rare variants are unlikely to lead to improved ability to predict disease risk and therapeutic response. Epistasis (gene-gene interaction) and pleiotropy (diverse effects of the same gene) are known to play major roles in the genetic architecture of complex traits in model organisms, but have not yet been explored in human biology. This project aims to overcome this challenge by studying autism traits in congenital disorders of the Ras-MAPK signaling pathway. Ras-MAPK diseases are genetic disorders with known mutations that include effects on craniofacial, cardiac, cutaneous, musculoskeletal and ocular development, as well as carrying increased risk of cancer and varying expression of neurocognitive impairment. Preliminary data show that these disorders are strongly associated with autism and that common polymorphisms in the same genes are associated with idiopathic familial autism. Autism-related traits will be measured in subjects with Ras-MAPK disorders followed by genome-wide mapping for interactors with the known Ras-MAPK genes. Then induced pluripotent stem cell models from fibroblasts of patients with these disorders will be established in order to investigate expression and functional assays utilizing cells differentiated into varying fates. This project could further understanding of how genetic variants mediate disease risk and improve diagnosis, prognosis, prevention and treatment options for autism. Project Status


Funder National Institutes of Health
Fiscal Year Funding $2,317,500.00
Current Award Period 2010-2015
Project Number 1DP2OD007449-01
Principal Investigator Weiss, Lauren
Received ARRA Funding? No
Strategic Plan Question Question 3: What Caused This To Happen And Can This Be Prevented? (Causes)
Subcategory Genetic Risk Factors
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 3SA. Coordinate and implement the inclusion of approximately 20,000 subjects for genome-wide association studies, as well as a sample of 1,200 for sequencing studies to examine more than 50 candidate genes by 2011. Studies should investigate factors contributing to phenotypic variation across individuals that share an identified genetic variant and stratify subjects according to behavioral, cognitive, and clinical features. IACC Recommended Budget: $43,700,000 over 4 years.
Federal or Private? Federal
Institution University of California, San Francisco
State/Country California
Web Link 1 Dissecting epistasis and pleiotropy in autism towards personalized medicine (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
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