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Discovery of Functional Variants in Type 2 Diabetes Genes in Mexican Americans

Award Number: U01DK085524
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2009
PERIOD OF PERFORMANCE END DATE: 04/30/2023

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Discovery of Functional Variants in Type 2 Diabetes Genes in Mexican Americans - DESCRIPTION (provided by applicant): Type 2 diabetes is a major public health concern. Diabetes currently affects 25.8 million people in the US alone, 90-95% of all cases are type 2 and it disproportionately affects ethnic minorities in the US, including Mexican Americans. There are many microvascular and macrovascular complications related to diabetes, including a significantly increased risk of heart disease and stroke, blindness, kidney failure and kidney disease, neuropathy, and retinopathy. Several risk factors predispose individuals to the development of this disease including demographic characteristics like sex, age and ethnicity; and behavioral and lifestyle-related modifications. In addition, metabolic determinants such as impaired glucose tolerance and insulin resistance increase the risk of an individual progressing to type 2 diabetes. There have been continued efforts to localize and characterize T2D susceptibility genes using genome-wide linkage and genome-wide association study approaches, aside from the traditional candidate gene approach. Although linkage studies have identified various T2D susceptibility loci, subsequent gene discovery successes from such efforts have been limited. In recent years, the GWAS method has become a popular design with unprecedented successes in localization of several novel T2D susceptibility loci, however, these common variants explain only about 10% of the total heritability indicating more loci remain to be identified. This has led to an increased interest in the potential role of rare variants in common complex diseases. As one of the five research groups involved in the T2D-GENES consortium, the data obtained from our San Antonio Mexican American Family Studies (SAMAFS) have contributed to the two major projects of T2D- GENES. This proposal, submitted in response to the RFA-DK-14-003 (AMP T2D-GENES consortium) aims to build on and expand the research activities of the T2D-GENES consortium. We will (i) expand the WGS data with an additional (already available) 1,000 whole genomes from SAMAFS to reaffirm the already found rare and private variant associations with T2D and glucose traits in Mexican Americans; and replicate selected rare association findings in other cohorts; (ii) recall approximately 300 (100 T2D and 200 non-T2D) SAMAFS participants from families carrying rare or private variants to perform deep phenotyping in which we will collect metabolic information, 3 tissues (muscle, fat, and PBMCs) for gene expression analysis and metabolomic profiling; and (iii) directly identify putative regulatory variants in gene regions of interest influencing T2D and perform preliminary functional assessment of associated variants, both rare and common. The estimated economic burden of diabetes in the United States alone is approximately $245 billion per year, making this disease of major public health importance. The ability to identify genes that are causally involved in disease risk provides an unparalleled opportunity to quickly determine biological pathways that are involved in disease pathology. A better understanding of the genetic contribution to diabetes development will provide novel approaches for the characterization, treatment and potential prevention of this costly disease.


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 = -$23,828 )
2024	2019	THE UNIVERSITY OF TEXAS RIO GRANDE VALLEY	1201 W UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	12/29/2023	NON-COMPETING CONTINUATION	-$23,828
														Subtotal = -$23,828

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2019	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	1/4/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	3/31/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	3/12/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $322,775 )
2019	2019	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	6/28/2019	NON-COMPETING CONTINUATION	$322,775
2019	2018	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	11/27/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $322,775

Issue Date FY: 2018 ( Subtotal = $583,186 )
2018	2018	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	6/13/2018	NON-COMPETING CONTINUATION	$583,186
														Subtotal = $583,186

Issue Date FY: 2017 ( Subtotal = $565,032 )
2017	2017	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	8	6/16/2017	NON-COMPETING CONTINUATION	$56,503
2017	2017	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	8	5/16/2017	NON-COMPETING CONTINUATION	$508,529
2017	2016	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	12/8/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$621,291
2017	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	12/8/2016	COMPETING CONTINUATION	-$621,291
														Subtotal = $565,032

Issue Date FY: 2016 ( Subtotal = $565,032 )
2016	2016	UNIVERSITY OF TEXAS RIO GRANDE VALLEY (UTRGV)	1201 W. UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	6/27/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$565,032
2016	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	7/11/2016	COMPETING CONTINUATION	$0
														Subtotal = $565,032

Issue Date FY: 2015 ( Subtotal = $734,026 )
2015	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	4/15/2015	COMPETING CONTINUATION	$734,026
2015	2013	TEXAS BIOMEDICAL RESEARCH INSTITUTE	7620 NORTHWEST LOOP 410	SAN ANTONIO	TX	78227	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/14/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $734,026

Issue Date FY: 2013 ( Subtotal = $674,163 )
2013	2013	TEXAS BIOMEDICAL RESEARCH INSTITUTE	7620 NORTHWEST LOOP 410	SAN ANTONIO	TX	78227	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	8/13/2013	NON-COMPETING CONTINUATION	$674,163
														Subtotal = $674,163

Issue Date FY: 2012 ( Subtotal = $879,580 )
2012	2012	TEXAS BIOMEDICAL RESEARCH INSTITUTE	7620 NORTHWEST LOOP 410	SAN ANTONIO	TX	78227	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	8/27/2012	NON-COMPETING CONTINUATION	$879,580
														Subtotal = $879,580

Issue Date FY: 2011 ( Subtotal = $515,276 )
2011	2011	TEXAS BIOMEDICAL RESEARCH INSTITUTE	7620 NORTHWEST LOOP 410	SAN ANTONIO	TX	78227	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/15/2011	NON-COMPETING CONTINUATION	$515,276
														Subtotal = $515,276

Issue Date FY: 2010 ( Subtotal = $504,080 )
2010	2010	SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH	7620 NORTHWEST LOOP 410	SAN ANTONIO	TX	78227	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	2	9/8/2010	NON-COMPETING CONTINUATION	$504,080
2010	2009	SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH	7620 NORTHWEST LOOP 410	SAN ANTONIO	TX	78227	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	11/20/2009	NEW	$0
2010	2009	SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH	7620 NORTHWEST LOOP 410	SAN ANTONIO	TX	78227	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	10/23/2009	NEW	$0
2010	2009	SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH	7620 NORTHWEST LOOP 410	SAN ANTONIO	TX	78227	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	1/8/2010	NEW	$0
														Subtotal = $504,080

Issue Date FY: 2009 ( Subtotal = $511,506 )
2009	2009	SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH	7620 NORTHWEST LOOP 410	SAN ANTONIO	TX	78227	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/14/2009	NEW	$511,506
2009	2009	SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH	7620 NORTHWEST LOOP 410	SAN ANTONIO	TX	78227	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	10/20/2009	NEW	$0
														Subtotal = $511,506

Grand Total All Awards = $5,830,828

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Discovery of Functional Variants in Type 2 Diabetes Genes in Mexican Americans

Award Number: U01DK085524

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/20/2009

PERIOD OF PERFORMANCE END DATE: 04/30/2023

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