Tuesday, July 1, 2025 7/1/2025

The CHARGE Study Phase II: A Multifactorial Approach to Autism Etiology

Award Number: R01ES031701
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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The CHARGE Study Phase II: A Multifactorial Approach to Autism Etiology - Abstract: This project builds upon 15 years of the CHARGE Study, which identified numerous environmental chemicals, nutritional factors, and maternal health conditions that are associated with altered risk for autism spectrum disorder (ASD). This work provided clues about potential pathogenic mechanisms and also produced the first evidence of gene-by-environment (GxE) interaction. In this renewal, CHARGE study will continue to enroll in order to achieve a solid sample size for statistically powerful analyses of both chemical mixtures and GxE interactions. Risk factors of concern are preeclampsia, air pollution, and pesticides, each having replicated evidence of association with ASD. This application departs from the focus on single exposures in isolate, and instead emphasizes multifactorial causation: the focus is on mixtures and interactions. In aim 1, state-of-the-art methods will be applied to understand the impact of exposure mixtures on risk for ASD and if feasible, to identify which component(s) of the mixture most contributes to the overall effects. Aims 2 and 3 address interactions between genes and non-genetic factors (GxE). Aim 2 is to identify common gene variants carried by the mother, which, in combination with early life environmental or medical factors, amplify the risk for ASD, more so than when either factor is assessed separately. The Precision Medicine Array from the Affymetrix platform will be used to generate over 800,000 SNPs that draw heavily from metabolic, pharmacologic, and immune-related regions of the genome. This project then pre-selects subsets of genes biologically relevant to the activity or mechanism of toxicity of each exposure, using annotated gene ontology databases. The resulting GxE analyses are expected to identify common variants that act synergistically with environmental insults, which may have been unremarkable in gene-only studies, or gene studies that emphasized rare variants. Aim 3 examines GxE interactions as in Aim 2, for the child's gene variants. To our knowledge, this will be the first study to evaluate GxE interaction utilizing omics-scale genetics data in a sufficiently powered analysis for detecting interactions. The proposed work moves autism etiologic research into a new direction that bridges separate silos of genetic and environmental research, creating a dynamic interdisciplinary and integrative science. Given shared biologic pathways between some genes and certain environmental exposures, the proposed project has potential to advance etiologic research towards targeted interventions that could reduce risk for ASD or ASD-associated disabilities and improve lives of affected individuals and their families. Additional significance may derive from identification of common variants that have hitherto eluded the traditional genetics enterprise. The long-term impacts may therefore be the emergence of a shift in etiologic research that unifies fragmented disciplinary approaches; major advancement in understanding common variants; and the possibility for public health precision interventions that expand notions of genetic susceptibility to encompass the biochemical milieu of the intrauterine and broader postnatal environment.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $1,586,759 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Environmental Health	000	5	2/17/2025	NON-COMPETING CONTINUATION	$1,586,759
														Subtotal = $1,586,759

Issue Date FY: 2024 ( Subtotal = $1,594,617 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Environmental Health	000	4	1/29/2024	NON-COMPETING CONTINUATION	$1,594,617
														Subtotal = $1,594,617

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Environmental Health	000	3	1/25/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $1,619,998 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Environmental Health	000	3	2/10/2022	NON-COMPETING CONTINUATION	$1,619,998
														Subtotal = $1,619,998

Issue Date FY: 2021 ( Subtotal = $1,707,651 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Environmental Health	000	2	2/5/2021	NON-COMPETING CONTINUATION	$1,707,651
														Subtotal = $1,707,651

Issue Date FY: 2020 ( Subtotal = $1,765,846 )
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Environmental Health	000	1	4/30/2020	NEW	$1,765,846
														Subtotal = $1,765,846

Grand Total All Awards = $8,274,871

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The CHARGE Study Phase II: A Multifactorial Approach to Autism Etiology

Award Number: R01ES031701

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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