# Genetic and Environmental risk of NAFLD-related HCC In All Latinos: the GENIAL Study

> **NIH NIH U01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $329,649

## Abstract

The burden of hepatocellular carcinoma (HCC) due to non-alcoholic fatty liver disease (NAFLD) has increased
substantially over the past two decades. Although both NAFLD and HCC disproportionately affect Latino
individuals, few Latinos were included in genetic and epidemiologic studies evaluating HCC risk. Prior genetic
studies examining NAFLD risk that did include Latinos were limited in that they used candidate-gene approaches
which cannot detect novel genetic associations. Other studies limited inclusion to individuals from one country,
and thus could not consider how the incredible diversity among Latinos might drive genetic risk or differences in
NAFLD phenotype, risk of cirrhosis, or HCC risk. In the proposed study, Drs. Jones and Flores will work
collaboratively as multiple principal investigators. Along with co-investigators, they will collaborate with other
members of the Liver Cirrhosis Network (LCN) to develop precise, personalized approaches to NAFLD
prognostication and HCC risk stratification targeted specifically to Latinos, a vulnerable population with excess
disease burden. In Aim 1, Drs. Flores and Jones will leverage existing data from two studies (UCLA ATLAS
Community Health Initiative and NIH All of Us Research Program) to conduct a genome wide association study
(GWAS), phenome-wide association study, and create polygenic risk scores in persons with NAFLD. All of Us
and ATLAS aim to enroll diverse participants to ensure inclusivity and generalizability in Precision Medicine
research. As such, the proposed study represents the largest, most racially diverse GWAS in NAFLD with 21,199
individuals with NAFLD already identified. We will define the relationship between known and novel single
nucleotide polypmorphisms (SNPs) and risk of NAFLD, NASH, NAFLD-cirrhosis, and NAFLD-HCC, stratified by
race, region of origin and genetic ancestry. In collaboration with LCN investigators, Drs. Flores and Jones will
enroll Latino participants with NAFLD into a prospective case-control study that aims to characterize gene-
environment interactions between known and novel genetic NAFLD-associated SNPs and environmental risk
factors including HIV, diabetes, and metabolic syndrome. They will engage new and existing LCN Cohort
participants as well as participants enrolled in existing cohorts at the University of Miami (UM), the University of
Los Angeles California (UCLA) and the University of Puerto Rico Comprehensive Cancer Center (UPRCCC). All
sites will identify and recruit new cases with NAFLD and healthy controls. We will develop polygenic risk scores
that incorporate genetic, clinical, sociocultural, behavioral, and environmental characteristics to predict (1) risk
of cirrhosis in persons with NAFLD, (2) hepatic decompensation in NAFLD patients with cirrhosis, and (3) HCC
risk in NAFLD patients with or without cirrhosis. NAFLD is the fastest growing cause of cirrhosis in the US and
disproportionately impacts Latinos who also have the highest HC...

## Key facts

- **NIH application ID:** 10932985
- **Project number:** 5U01CA288421-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Yvonne Nicole Flores
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $329,649
- **Award type:** 5
- **Project period:** 2023-09-21 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932985

## Citation

> US National Institutes of Health, RePORTER application 10932985, Genetic and Environmental risk of NAFLD-related HCC In All Latinos: the GENIAL Study (5U01CA288421-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932985. Licensed CC0.

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