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Integrated exposome profiling to identify environmental risk factors of metabolic disease in mid- and late-life

Award Number: R01ES035087
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: 03/17/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Integrated exposome profiling to identify environmental risk factors of metabolic disease in mid- and late-life - PROJECT SUMMARY/ABSTRACT Exposure to environmental chemicals may play an important role in the pathogenesis of type-2 diabetes (T2D) and metabolic syndrome (MetS) as these exposures are widespread in the population, and the prevalence of these metabolic disorders has dramatically increased over the past several decades. In the US, >42,000 types of chemicals are actively produced, but only a handful of chemicals are tested for their toxicity. Epidemiologic studies have also been restricted to a few targeted metabolism-disrupting chemicals, while relatively little is known about the potential metabolic toxicity of the majority of these chemicals. Analyses spanning wide classes of chemicals are critically needed to identify novel areas of risk, as well as specific associations with metabolic phenotypes. In addition, the underlying biological mechanisms linking environmental chemicals and T2D and MetS are still not well understood. Although risk assessment is critical for early detection and prevention of T2D and MetS, current risk prediction models generally use only a few known risk factors such as demographics, clinical measures including fasting blood glucose and body mass index, and family history and susceptible genotypes. Integrated exposomic signatures may improve risk stratification/discrimination to identify vulnerable populations and provide a more effective intervention approach at the individual- and population-level (i.e., precision health). To address these scientific gaps, we propose to conduct an exposome- metabolome wide association study in relation to incident T2D and Mets in the Study of Women’s Health Across the Nation (SWAN), a multi-racial/ethnic longitudinal cohort of women from midlife to late-life. Using untargeted, high-resolution mass spectrometry that provides the high-quality measures needed for sequencing the human blood exposome, we aim to establish a new paradigm for environmental health research addressing metabolic disease risk. This can be achieved by taking advantage of the rich longitudinal features of the SWAN. Specifically, we aim to 1) conduct an integrated exposome- and metabolome-wide association study of incident T2D and MetS using pre-diagnosis blood samples collected at baseline to characterize known and novel environmental exposures detected using untargeted high-resolution mass spectrometry linked to future T2D and MetS risk and identify endogenous metabolite and disease-associated alterations underlying T2D and MetS; 2) evaluate temporal evolution of exposome and metabolome profiles in T2D and MetS cases and metabolically healthy controls; 3) identify pre-diagnostic metabolomic signatures that link targeted exposures of metabolism disrupting chemicals and novel exposome biomarkers to incident T2D and MetS; and 4) develop and validate exposome-based risk prediction models for T2D and MetS. Successful completion of these aims will identify critical pre-diagnostic exposome biomarkers that may improve risk prediction for T2D and MetS.


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: 2026 ( Subtotal = $581,060 )
2026	2026	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Environmental Health	000	4	12/31/2025	NON-COMPETING CONTINUATION	$581,060
														Subtotal = $581,060

Issue Date FY: 2025 ( Subtotal = $615,228 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Environmental Health	000	3	12/30/2024	NON-COMPETING CONTINUATION	$615,228
														Subtotal = $615,228

Issue Date FY: 2024 ( Subtotal = $613,991 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Environmental Health	000	2	1/25/2024	NON-COMPETING CONTINUATION	$613,991
														Subtotal = $613,991

Issue Date FY: 2023 ( Subtotal = $669,397 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Environmental Health	000	1	3/17/2023	NEW	$669,397
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Environmental Health	001	1	4/14/2023	NEW	$0
														Subtotal = $669,397

Grand Total All Awards = $2,479,676

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Integrated exposome profiling to identify environmental risk factors of metabolic disease in mid- and late-life

Award Number: R01ES035087

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: 03/17/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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