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Arsenic and the Human Genome: susceptibility and response to exposure

Award Number: R35ES028379
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: 09/15/2017
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Arsenic and the Human Genome: susceptibility and response to exposure - PROJECT SUMMARY Arsenic contamination of food and drinking water is a serious global health issue in the U.S. and worldwide. Arsenical skin lesions are a common and early sign of arsenic toxicity, but exposure to arsenic is also associated with risk for various types of cancer, cardiovascular disease, non-malignant respiratory disease, and shortened life span. A major focus of epidemiological research on arsenic exposure has been understanding genetic susceptibility to arsenic toxicity. Genetic studies have discovered roles for both inherited variation (e.g., AS3MT variants) as well as dynamic features of the genome (i.e., telomere length) in susceptibility to arsenic toxicity and response to exposure. Additional research is needed to fully understand these gene-environment relationships. The last decade of research on genetic susceptibility to disease in humans has clearly demonstrated that large studies with genome-wide measurement are highly likely to deliver discoveries that are re-producible. Thus, we propose creating a large genomic data resource in the context of an epidemiological study of arsenic exposure in rural Bangladesh. We will use this resource to identify the features of the human genome that reflect susceptibility or response to arsenic exposure. Our first goal is to extend our ongoing work on the genetics of arsenic metabolism efficiency (AME) and GxE (gene-by- environment interaction) to identify inherited variants that influence arsenic metabolism or arsenic toxicity. Under this goal, we will investigate the biological mechanisms of arsenic-related variants and evaluate the utility genetic information for exposure reduction. Achieving this goal will entail activities such as genome-wide association and heritability studies of AME and arsenical skin lesion risk, genome-wide searches for GxE, estimating the effects of SNPs on arsenic-related health outcomes, and evaluating the impact of returning genetic results to participants on exposure-related behaviors. Our second goal is to extend or our work on arsenic and telomere length to identify additional dynamic features of the genome that reflect biological response to arsenic or susceptibility to arsenic toxicity. Achieving this goal will entail testing numerous genomic features for association with arsenic exposure and arsenical skin lesion status, including somatic chromosomal losses and point mutations, DNA methylation, epigenetic aging, and mitochondrial DNA mutation and copy number. If successful, this project will provide novel biomarkers of susceptibility and toxicity as well as biomarkers of the biological effects of arsenic exposure. The biomarkers identified will provide information useful for (1) identifying subgroups of highly susceptible individuals, (2) understanding biological mechanisms underlying susceptibility and toxicity, and (3) motivating susceptible individuals to reduce their exposure. Furthermore, we will continue developing technologies for targeted measurement of copy number variable regions for large scale epidemiological and environmental health research. This work has the potential to have transformative impact not only on knowledge, but also on both global and local environmental health.


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: 2024 ( Subtotal = $804,122 )
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	003	8	8/21/2024	NON-COMPETING CONTINUATION	$618,211
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	004	8	8/22/2024	SUPPLEMENT FOR EXPANSION	$119,020
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	000	7	2/13/2024	SUPPLEMENT FOR EXPANSION	$66,891
2024	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	002	7	6/6/2024	NON-COMPETING CONTINUATION	$0
2024	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	001	7	4/30/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $804,122

Issue Date FY: 2023 ( Subtotal = $662,408 )
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	003	7	8/1/2023	SUPPLEMENT FOR EXPANSION	$27,465
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	002	7	7/31/2023	NON-COMPETING CONTINUATION	$634,943
2023	2022	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	001	6	6/16/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	000	6	1/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $662,408

Issue Date FY: 2022 ( Subtotal = $791,875 )
2022	2022	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	000	5	1/6/2022	SUPPLEMENT FOR EXPANSION	$56,610
2022	2022	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	001	6	7/22/2022	NON-COMPETING CONTINUATION	$651,188
2022	2022	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	002	6	7/23/2022	SUPPLEMENT FOR EXPANSION	$84,077
														Subtotal = $791,875

Issue Date FY: 2021 ( Subtotal = $666,959 )
2021	2021	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	000	5	7/27/2021	NON-COMPETING CONTINUATION	$666,959
														Subtotal = $666,959

Issue Date FY: 2020 ( Subtotal = $760,753 )
2020	2020	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	000	4	7/29/2020	NON-COMPETING CONTINUATION	$760,753
														Subtotal = $760,753

Issue Date FY: 2019 ( Subtotal = $740,898 )
2019	2019	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	000	3	7/29/2019	NON-COMPETING CONTINUATION	$662,416
2019	2019	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	001	3	7/30/2019	SUPPLEMENT FOR EXPANSION	$78,482
														Subtotal = $740,898

Issue Date FY: 2018 ( Subtotal = $793,706 )
2018	2018	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	001	2	8/3/2018	SUPPLEMENT FOR EXPANSION	$119,956
2018	2018	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	000	2	6/28/2018	NON-COMPETING CONTINUATION	$673,750
														Subtotal = $793,706

Issue Date FY: 2017 ( Subtotal = $329,882 )
2017	2017	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Environmental Health	000	1	9/5/2017	NEW	$329,882
														Subtotal = $329,882

Grand Total All Awards = $5,550,603

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Arsenic and the Human Genome: susceptibility and response to exposure

Award Number: R35ES028379

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: 09/15/2017

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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