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Identification of the Exposome in Fatty Liver Disease in Mexican American Families Using Genetic Correction

Award Number: R01MD012564
ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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PROJECT SUMMARY Fatty liver disease (FLD) is a major public health issue affecting millions of people worldwide. Chronic FLD is defined by excess liver fat (hepatic steatosis) and can lead to a more profound disease state of steatohepatitis (SH) that may be reflected in hepatic fibrosis (including severe cirrhosis at the extreme). SH can lead to liver failure or hepatocellular carcinoma (HCC). Multiple risk factors predispose individuals to the development of FLD including biological factors (obesity, insulin resistance, type 2 diabetes) demographic characteristics (e.g. sex, age and ethnicity), behavioral and lifestyle-related variables (e.g., alcohol intake, dietary behavior and physical activity), and both endogenous (e.g., infectious agents such as hepatitis viruses, microbiome variability) and exogenous environmental factors (e.g., exposure to pollutants/contaminants/toxins). Mexican Americans are disparately impacted by nonalcoholic FLD with some of the highest observed prevalences in the world and exhibit a prevalence of cirrhosis that is 9 times the national average. Although there is a heritable component of FLD risk, the dramatic increase FLD and HCC prevalence over the past 20 years clearly points to a major role for environmental factors since genetic variation is effectively constant on such a timescale. In this project, we will use high-dimensional omic characterization of Mexican Americans living in South Texas to assess the FLD-relevant environmentally determined exposome. We will recruit 1,000 participants from the longitudinal San Antonio Mexican American Family Study (SAMAFS) to undergo magnetic resonance imaging (MRI) to obtain measures of liver fat and liver fibrosis. Each participant has previously been completely genetically characterized by whole genome sequencing, and the WGS data will be employed to optimally identify the exposome for FLD risk in a minority population. To achieve these objectives, we will: (I) perform MRI-based measures of liver fat/fibrosis and omic characterization of 1,0000 individuals from large extended SAMAFS pedigrees, including metabolomic profiling, lipidomic profiling, epigenomic analysis, and transcriptomic sequencing; (II) detect environmental effects on FLD risk using a novel statistical genetic approach to maximize systematic environmental signals and search for environmental factors reflected in high-dimensional metabolomic/lipidomic, epigenomic, and transcriptomic biomarkers that are correlated with FLD risk; (III) characterize/classify environmental signals with regard to major environmental domains through the identification of non-random spatial distribution, or correlation with known components such as dietary behavior, socioeconomic factors, exogenous exposures, etc.; (IV) detect genotype x environment interactions using the omic data to detect genetic factors involved in the differential response of FLD risk to novel environmental factors. Overall, the ability to identify novel environmental determinants of chronic liver disease risk in an ethnic minority population provides a major opportunity to speed the development of improved targeted treatments.


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 = $0 )
2024	2022	THE UNIVERSITY OF TEXAS RIO GRANDE VALLEY	1201 W UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Minority Health and Health Disparities Research	000	5	12/5/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $726,132 )
2022	2022	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Minority Health and Health Disparities Research	001	5	4/17/2022	NON-COMPETING CONTINUATION	$72,614
2022	2022	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Minority Health and Health Disparities Research	000	5	11/16/2021	NON-COMPETING CONTINUATION	$653,518
														Subtotal = $726,132

Issue Date FY: 2021 ( Subtotal = $728,588 )
2021	2021	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Minority Health and Health Disparities Research	001	4	3/11/2021	NON-COMPETING CONTINUATION	$72,859
2021	2021	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Minority Health and Health Disparities Research	000	4	11/23/2020	NON-COMPETING CONTINUATION	$655,729
														Subtotal = $728,588

Issue Date FY: 2020 ( Subtotal = $739,998 )
2020	2020	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Minority Health and Health Disparities Research	001	3	1/3/2020	NON-COMPETING CONTINUATION	$74,000
2020	2020	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Minority Health and Health Disparities Research	000	3	11/14/2019	NON-COMPETING CONTINUATION	$665,998
														Subtotal = $739,998

Issue Date FY: 2019 ( Subtotal = $739,578 )
2019	2019	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Minority Health and Health Disparities Research	000	2	11/15/2018	NON-COMPETING CONTINUATION	$739,578
														Subtotal = $739,578

Issue Date FY: 2018 ( Subtotal = $751,281 )
2018	2018	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Minority Health and Health Disparities Research	000	1	4/27/2018	NEW	$676,153
2018	2018	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Minority Health and Health Disparities Research	001	1	6/29/2018	NEW	$75,128
														Subtotal = $751,281

Grand Total All Awards = $3,685,577

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Identification of the Exposome in Fatty Liver Disease in Mexican American Families Using Genetic Correction

Award Number: R01MD012564

ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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