Association of Genetic Risk Score With NAFLD in An Ethnically Diverse Cohort
Jun Wang1, David V Conti1,2,3, David Bogumil1
1Department of Preventive MedicineKeck School of Medicine of University of Southern CaliforniaLos AngelesCAUSA.
Hepatology Communications
|September 24, 2021
Summary
This study validated genetic risk variants for nonalcoholic fatty liver disease (NAFLD) across diverse ethnicities. A genetic risk score (GRS) effectively stratified NAFLD risk, particularly in those with cirrhosis.
Area of Science:
- Genetics
- Hepatology
- Population Health
Background:
- Nonalcoholic fatty liver disease (NAFLD) genetic research predominantly features White populations.
- Understanding genetic contributions to NAFLD across diverse ethnic groups is crucial for equitable healthcare.
Purpose of the Study:
- To assess the generalizability of known NAFLD genetic variants in an ethnically diverse cohort.
- To develop and validate a genetic risk score (GRS) for NAFLD across multiple ethnic groups.
- To investigate the association of the GRS with NAFLD, considering cirrhosis status.
Main Methods:
- A nested case-control study analyzed 1,448 NAFLD cases and 8,444 controls from a multi-ethnic cohort.
- Thirty genome-wide association study (GWAS) single nucleotide polymorphisms (SNPs) and 17 additional NAFLD-associated variants were examined.
- An 11-SNP weighted GRS was constructed and its association with NAFLD risk was evaluated across ethnic groups and cirrhosis status.
Main Results:
- Twenty of 30 GWAS SNPs (67%) were replicated in the pooled multi-ethnic population, with higher replication in Latinos (43%) and Japanese Americans (37%).
- Key genes like PNPLA3, HSD17B13, and TM6SF2 showed replication across multiple ethnic groups.
- The 11-SNP GRS significantly associated with NAFLD risk across all ethnic groups (OR 1.41) and was stronger for NAFLD with cirrhosis (OR 1.67).
Conclusions:
- Several key genetic variants for NAFLD are transportable across diverse ethnic groups.
- A multi-ethnic GRS demonstrates utility in stratifying NAFLD risk, including in individuals with cirrhosis.
- These findings support the broader application of genetic risk prediction for NAFLD in varied populations.
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