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

> **NIH NIH R01** · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · 2020 · $739,998

## Abstract

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 envi...

## Key facts

- **NIH application ID:** 9824476
- **Project number:** 5R01MD012564-03
- **Recipient organization:** UNIVERSITY OF TEXAS RIO GRANDE VALLEY
- **Principal Investigator:** John Blangero
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $739,998
- **Award type:** 5
- **Project period:** 2018-04-27 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9824476

## Citation

> US National Institutes of Health, RePORTER application 9824476, Identification of  the Exposome in Fatty Liver Disease in Mexican American Families Using Genetic Correction (5R01MD012564-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9824476. Licensed CC0.

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