The MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) Study was launched in 2006 by the UC Davis MIND Institute and Center for Children's Environmental Health as the first epidemiologic cohort of younger siblings of children with autism spectrum disorders (ASD) to begin follow-up during (and before) the prenatal period when ASD and other neurodevelopmental outcomes are likely to originate.1-7 In contrast to population-based cohorts, which require very large sample sizes given a relatively low prevalence of ASD (currently 1 in 68)8 and typically are not able to conduct gold standard diagnosis of ASD, the enriched risk design takes advantage of participants at exceptionally high risk for developing ASD and other neurodevelopmental outcomes, achieving tremendous efficiencies. Previous cohorts of high-risk younger siblings recruited postnatally have not addressed non-inherited and potentially modifiable etiologic factors.9 Early enrollment provides an opportunity to examine a broad array of environmental exposures and their mechanisms, while simultaneously allowing thorough search for early biologic markers.10 Given increasing prevalence of ASD,8,11 it is more critical now than ever to invest in studies identifying emerging environmental factors responsible for increasing risk of these neurodevelopmental disorders and the mechanisms underlying their etiology, which are currently not well-understood. This project addresses both gaps by maintaining and enhancing the resource infrastructure of the MARBLES enriched-risk cohort. Retention of this cohort with deep evaluation of risk factors, mechanistic markers, and outcomes will be critical to evaluation and early identification of newly emerging etiologic factors for ASD in a susceptible population, serving as a canary in a coal-mine for identifying exposures that influence neurodevelopment. Our cohort's data and specimens will permit analyses of new questions on exposures in relation to well-defined clinical neurodevelopmental outcomes, and our rich characterization of mechanistic biomarkers could identify pathways and signatures of susceptibility involved. We propose to continue to enroll and follow-up participants of one of the only enriched-risk ASD U.S. cohorts with prospectively collected pregnancy data and biosamples that is currently in no cost extension (NCE). In addition, we propose to further develop and maintain our repository infrastructure for the expansive data and sample repositories in order to expand collaborative sharing and facilitate investigation of newly-emerging environmental exposures and molecular mechanistic markers in relation to risk and presentation of ASD and other adverse neurodevelopmental conditions. Finally, we plan to validate and reliability test environmental exposure questions and measures for use in future studies. Completion of these aims will assist collaborative sharing of our vast collection of data and biosamples to facilitate investigation of newly-emerging environmental exposures and molecular mechanistic markers in relation to risk and presentation of ASD and other adverse neurodevelopmental conditions.

Public Health Relevance

Given increasing prevalence of ASD, it is more critical now than ever to invest in studies identifying emerging environmental factors responsible for increasing risk of these neurodevelopmental disorders and the poorly understood mechanisms underlying their etiology. This project addresses both gaps by maintaining and enhancing the rich environmental and assessment data and vast sample repository and infrastructure of the MARBLES enriched-risk cohort to promoting resource sharing. This unique study population will be critical to evaluation and early identification of newly emerging etiologic factors for ASD in a susceptible population, serving as a canary in a coal-mine for identifying exposures that influence neurodevelopment. Further, results of environmental exposure reliability, variability, and validity assessments will inform and advance future studies of environmental factors during pregnancy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Resource-Related Research Projects (R24)
Project #
5R24ES028533-02
Application #
9569654
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Gray, Kimberly A
Project Start
2017-09-30
Project End
2022-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Davis
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Dou, John; Schmidt, Rebecca J; Benke, Kelly S et al. (2018) Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation. Epigenetics 13:108-116