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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

Genome-wide examination of DNA methylation in autism

Principal Investigator

Principal Investigator

Fallin, Dani

Description

Description

Previous studies have estimated that autism (ASD) is highly heritable, i.e., many of ASDs clinical attributes can be explained by genetics. However, no single causal gene has yet been identified. Although several genetic variants are associated with autism, they account for a relatively small proportion of the estimated heritability and none has been definitively confirmed. This paradox may be explained by the inter-dependency between particular genetic sequences and specific environmental exposures, often referred to as gene-environment interaction (GxE). Growing evidence suggests environmental exposures, especially prenatal, are risk factors for autism. Thus, it is important to examine genetic variation in the context of environmental exposures and to identify potential mechanisms for GxE in autism. This is the primary objective of the current study. Although every cell in the human body has essentially the same DNA sequence, they have very different and specific functions. Cell type-specific functions arise from different sets of genes being turned on or off, i.e., cells run different gene expression programs. DNA methylation (DNAm), a reversible chemical modification of DNA, is a way for cells to regulate their gene expression program without changing their DNA sequence. There is growing evidence that DNAm is susceptible to environmental exposures, providing a physical link between environmental risk factors and genetics. Identification of DNAm differences (whether due to genetic or environmental factors) among children with and without ASD may elucidate a biological mechanism for GxE in ASD. The investigators will measure DNAm across the genome of 600 children (300 with ASD and 300 without) from The Study to Explore Early Development. The specific aims are to: 1) measure DNAm across the genome and identify differences based on (a) diagnosis, (b) genetic sequence, (c) prenatal environmental exposures, and (d) sites of GxE; 2) confirm prior findings using an independent method and set of samples; and 3) establish tissue-relevance by comparing prior results (from blood) to DNAm patterns obtained in a parallel study of brains from 30 ASD and 30 non-ASD individuals. Integration of genetic, DNAm, and environmental information enables the first comprehensive molecular analysis of potential GxE in autism, and may also identify modifiable risk factors and provide new diagnostic and therapeutic targets for ASD.

Funder

Funder

Autism Speaks

Fiscal Year Funding

Fiscal Year Funding

149999

Current Award Period

Current Award Period

2011-2014

Strategic Plan Question

Strategic Plan Question

Question 3: What Caused This To Happen And Can This Be Prevented?

Strategic Plan Objective

Strategic Plan Objective

Green dot: Objective has greater than or equal to the recommended funding. 3SJ. Support at least three studies that focus on the role of epigenetics in the etiology of ASD, including studies that include assays to measure DNA methylations and histone modifications and those exploring how exposures may act on maternal or paternal genomes via epigenetic mechanisms to alter gene expression, by 2012. IACC Recommended Budget: $20,000,000 over 5 years.

Project Link

Project Link

Genome-wide examination of DNA methylation in autism (External web link)

Institution

Institution

Johns Hopkins University

State/Country

State/Country

Maryland

Project Number

Project Number

7659

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Genome-wide examination of DNA methylation in autism | 0 | 2011 | 7659
Genome-wide examination of DNA methylation in autism | 149999 | 2012 | 7659
Genome-wide examination of DNA methylation in autism | 0 | 2015 | 7659
Genome-wide examination of DNA methylation in autism | 149999 | 2014 | 7659

 
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