ArticleJournal of hepatology2020
A common variant in PNPLA3 is associated with age at diagnosis of NAFLD in patients from a multi-ethnic biobank.
Article in Journal of hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 58 citations in OpenAlex.
- Evaluating a Polygenic Risk Score for Hepatocellular Carcinoma in Multiethnic Cirrhosis Patients in Texas.Cancer medicine · 2026Article
- Cancer Risk Among Young Adults With Clinically Diagnosed Fatty Liver Disease: A Nationwide Cohort Study in South Korea.Cancer medicine · 2026Article
- PNPLA3-I148M reduces hepatic triacylglycerol secretion and mitigates diet induced left ventricular diastolic dysfunction.Scientific reports · 2026Article
- Exploratory associations of candidate modifier variants with disease severity, age at onset, and drug response in three Wilson disease patients sharing the same ATP7B mutation.Molecular biology reports · 2026Article
- Genetic modulators of metabolic dysfunction-associated steatotic liver disease (MASLD) and their epistatic interactions: from in vitro and animal models to clinical outcomes.BMC medical genomics · 2026Review
- Multiscale Analysis of PNPLA2 and PNPLA3 Membrane Targeting.bioRxiv : the preprint server for biology · 2026Article
- Metabolic Dysfunction-Associated Steatotic Liver Disease Is Associated With Adverse Social Factors: An Analysis UsingGastro hep advances · 2026Article
- Hepatic GPR110 contributes to sex disparity in the development of MASH through oestrogen receptor α-dependent signalling.Nature metabolism · 2026Article
- Projected Trends in Metabolic Dysfunction-Associated Steatotic Liver Disease Mortality Through 2040.JAMA network open · 2025Article
- Parental liver disease mortality is associated with unfavorable outcomes in patients with alcohol-associated hepatitis.Hepatology communications · 2025Observational
- Design and rationale for a global novel non-invasive screening observational study using genetics and non-invasive methodologies to identify at-risk MASLD participants: The ALIGN study.Contemporary clinical trials communications · 2025Article
- Targeting PNPLA3 to Treat MASH and MASH Related Fibrosis and Cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Article
- Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort.BMC gastroenterology · 2025Article
- Unraveling Metabolic Dysfunction-Associated Steatotic Liver Disease Through the Use of Omics Technologies.International journal of molecular sciences · 2025Review
- Association between eGDR and MASLD and liver fibrosis: a cross-sectional study based on NHANES 2017-2023.Frontiers in medicine · 2025Article
- Predictivity of Hepatic Steatosis Index for Gestational Hypertension and Preeclampsia: a Prospective Cohort Study.International journal of medical sciences · 2025Article
- MASLD: What We Have Learned and Where We Need to Go-A Call to Action.Radiographics : a review publication of the Radiological Society of North America, Inc · 2024Review
- Are we ready for genetic testing in metabolic dysfunction-associated steatotic liver disease?United European gastroenterology journal · 2024Review
- Age, BMI, and Type 2 Diabetes Modify the Relationship Between PNPLA3 and Advanced Fibrosis in Children and Adults With NAFLD.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2024Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe Ile138Met variant (rs738409) in the PNPLA3 gene has the largest effect on non-alcoholic fatty liver disease (NAFLD), increasing the risk of progression to severe forms of liver disease. It remains unknown if the variant plays a role in age of NAFLD onset. We aimed to determine if rs738409 impacts on the age of NAFLD diagnosis.
methodsWe applied a novel natural language processing (NLP) algorithm to a longitudinal electronic health records (EHR) dataset of >27,000 individuals with genetic data from a multi-ethnic biobank, defining NAFLD cases (n = 1,703) and confirming controls (n = 8,119). We conducted i) a survival analysis to determine if age at diagnosis differed by rs738409 genotype, ii) a receiver operating characteristics analysis to assess the utility of the rs738409 genotype in discriminating NAFLD cases from controls, and iii) a phenome-wide association study (PheWAS) between rs738409 and 10,095 EHR-derived disease diagnoses.
resultsThe PNPLA3 G risk allele was associated with: i) earlier age of NAFLD diagnosis, with the strongest effect in Hispanics (hazard ratio 1.33; 95% CI 1.15-1.53; p <0.0001) among whom a NAFLD diagnosis was 15% more likely in risk allele carriers vs. non-carriers; ii) increased NAFLD risk (odds ratio 1.61; 95% CI 1.349-1.73; p <0.0001), with the strongest effect among Hispanics (odds ratio 1.43; 95% CI 1.28-1.59; p <0.0001); iii) additional liver diseases in a PheWAS (p <4.95 × 10
conclusionGiven the role of the rs738409 in NAFLD diagnosis age, our results suggest that stratifying risk within populations known to have an enhanced risk of liver disease, such as Hispanic carriers of the rs738409 variant, would be effective in earlier identification of those who would benefit most from early NAFLD prevention and treatment strategies. LAY SUMMARY: Despite clear associations between the PNPLA3 rs738409 variant and elevated risk of progression from non-alcoholic fatty liver disease (NAFLD) to more severe forms of liver disease, it remains unknown if PNPLA3 rs738409 plays a role in the age of NAFLD onset. Herein, we found that this risk variant is associated with an earlier age of NAFLD and other liver disease diagnoses; an observation most pronounced in Hispanic Americans. We conclude that PNPLA3 rs738409 could be used to better understand liver disease risk within vulnerable populations and identify patients that may benefit from early prevention strategies.
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