Background & Aims: Genetic variants affecting liver disease risk vary among racial and ethnic groups. Hispanics/Latinos in the United States have a high prevalence of PNPLA3 I148M, which increases liver disease risk, and a low prevalence of HSD17B13 predicted loss-of-function (pLoF) variants, which reduce risk. Less is known about the prevalence of liver disease–associated variants among Hispanic/Latino subpopulations defined by country of origin and genetic ancestry. We evaluated the prevalence of HSD17B13 pLoF variants and PNPLA3 I148M, and their associations with quantitative liver phenotypes in Hispanic/Latino participants from an electronic health record–linked biobank in New York City. Methods: This study included 8739 adult Hispanic/Latino participants of the BioMe biobank with genotyping and exome sequencing data. We estimated the prevalence of Hispanic/Latino individuals harboring HSD17B13 and PNPLA3 variants, stratified by genetic ancestry, and performed association analyses between variants and liver enzymes and Fibrosis-4 (FIB-4) scores. Results: Individuals with ancestry from Ecuador and Mexico had the lowest frequency of HSD17B13 pLoF variants (10%/7%) and the highest frequency of PNPLA3 I148M (54%/65%). These ancestry groups had the highest outpatient alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and the largest proportion of individuals with a FIB-4 score greater than 2.67. HSD17B13 pLoF variants were associated with reduced ALT level (P =.002), AST level (P <.001), and FIB-4 score (P =.045). PNPLA3 I148M was associated with increased ALT level, AST level, and FIB-4 score (P <.001 for all). HSD17B13 pLoF variants mitigated the increase in ALT conferred by PNPLA3 I148M (P =.006). Conclusions: Variation in HSD17B13 and PNPLA3 variants across genetic ancestry groups may contribute to differential risk for liver fibrosis among Hispanic/Latino individuals.

Original languageEnglish
JournalClinical Gastroenterology and Hepatology
StateAccepted/In press - 2023


  • Biobank
  • Electronic Health Records
  • FIB-4 Score
  • Genetic Risk
  • HSD17B13
  • Hispanic/Latino
  • Liver Fibrosis
  • PNPLA3


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