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Identifying Novel Biological Pathways for Gout using DNA Methylation and Genetics

Award Number: R01AR073178
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Identifying Novel Biological Pathways for Gout using DNA Methylation and Genetics - Abstract: Identifying Novel Biological Pathways for Gout using DNA Methylation and Genetics Gout is the most common form of inflammatory arthritis and affects ~8 million U.S. adults. Patients with gout experience intensely painful flares associated with impaired quality of life and high levels of healthcare utilization. With increasing prevalence of risk factors for gout, such as older age, obesity, hypertension, chronic kidney disease, and hyperuricemia, the incidence and prevalence of gout and its public health importance are all rising. However, gout is understudied compared to other rheumatologic conditions. Discovery of novel risk factors for gout can enhance our understanding of the disease susceptibility and identify targets for prevention and treatment. Gout attacks are inflammatory responses to the deposition of monosodium urate crystals in articular tissues causing rapidly intensifying painful and swollen joint(s). However, most individuals with hyperuricemia do not development gout. Our understanding of individual variation in susceptibility to acute gout is limited. The immune response is known to be involved in gout flares, including activation of the inflammasome. Emerging evidence supports links between inflammation and DNA methylation levels. However, factors influencing DNA methylation levels and their consequences for chronic disease remain to be elucidated. The examination of DNA methylation in whole blood has the potential to uncover epigenetic risk factor for gout. DNA methylation levels may also be intermediaries of environmental and genetic risk factors for gout and thus could yield insight into the biological pathways mediating gout flares or may serve as biomarkers for exposure to environmental risk factors. The overarching goal of this study is to uncover epigenetic factors that can illuminate the biological pathways underlying gout susceptibility and/or serve as biomarkers for the prediction of gout. Our aims are : (1) to identify DNA methylation sites associated with incident gout; (2) to identify DNA methylation sites associated with serum urate levels followed by (i) evaluating the potential causal relation between associated DNA methylation sites and serum urate using a Mendelian randomization approach, and (ii) an in-depth investigation of the urate-associated sites that have been linked to blood pressure; (3) to develop and validate risk prediction models for gout incorporating data from: (i) clinical, (ii) genetic and (iii) epigenetic risk factors, and examine how factors beyond serum urate levels add to risk prediction across sexes and over intermediate and longer time periods. This proposed study will accelerate research on gout prevention and treatment by identifying potentially reversible epigenetic factors related to incident gout and urate levels. The gout risk prediction models will lay the foundation for risk stratification strategy for future intervention trials for gout treatment and management, particularly among high- risk patients in whom treatment to serum urate target is particularly important.


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 = -$119,769 )
2024	2023	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	4/9/2024	NON-COMPETING CONTINUATION	-$119,769
														Subtotal = -$119,769

Issue Date FY: 2023 ( Subtotal = $329,342 )
2023	2023	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	4/18/2023	NON-COMPETING CONTINUATION	$32,933
2023	2023	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	11/30/2022	NON-COMPETING CONTINUATION	$296,409
														Subtotal = $329,342

Issue Date FY: 2022 ( Subtotal = $424,216 )
2022	2022	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	8/5/2022	NON-COMPETING CONTINUATION	$38,568
2022	2022	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	12/8/2021	NON-COMPETING CONTINUATION	$385,648
														Subtotal = $424,216

Issue Date FY: 2021 ( Subtotal = $464,493 )
2021	2021	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	005	4	5/17/2021	NON-COMPETING CONTINUATION	$33,519
2021	2021	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	4	12/14/2020	NON-COMPETING CONTINUATION	$430,974
2021	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	11/10/2020	NON-COMPETING CONTINUATION	$330,329
2021	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	11/10/2020	NON-COMPETING CONTINUATION	-$330,329
2021	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	2	1/8/2021	NON-COMPETING CONTINUATION	-$90,304
2021	2020	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	3	1/8/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$90,304
														Subtotal = $464,493

Issue Date FY: 2020 ( Subtotal = $580,174 )
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	2	5/15/2020	NON-COMPETING CONTINUATION	-$240,025
2020	2020	UNIVERISTY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	3	6/2/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$243,025
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	2	12/4/2019	NON-COMPETING CONTINUATION	$0
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	11/20/2019	NON-COMPETING CONTINUATION	$577,174
2020	2018	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	11/13/2019	NEW	$0
														Subtotal = $580,174

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/21/2019	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $670,298 )
2018	2018	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/21/2018	NEW	$670,298
														Subtotal = $670,298

Grand Total All Awards = $2,348,754

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Identifying Novel Biological Pathways for Gout using DNA Methylation and Genetics

Award Number: R01AR073178

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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