Evidence mapPaperPMID 40166930Full record

ReviewThe Journal of clinical investigation2025

Human genetics of metabolic dysfunction-associated steatotic liver disease: from variants to cause to precision treatment.

Vincent L Chen, Annapurna Kuppa, Antonino Oliveri, Yanhua Chen, Prabhu Ponnandy, Puja B Patel, Nicholette D Palmer, Elizabeth K Speliotes

Abstract readReview
In one paragraph

Review in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Steatotic liver disease in Latin America: current views and perspectives.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Journal of clinical medicine · 2026
    Article
  9. Article
  10. Article
  11. Review
  12. Genetic Information Enhances a Novel Non-Invasive Steatosis Index and Outperforms Existing Steatosis Indices.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Call a spade a spade.Hepatobiliary surgery and nutrition · 2025
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Vincent L ChenDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Annapurna KuppaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Antonino OliveriDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Yanhua ChenDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Prabhu PonnandyDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Puja B PatelDepartment of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Nicholette D PalmerDepartment of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Elizabeth K SpeliotesDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Funding

Pilot and Feasibility ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 to 2025
$4.9M
Integrative Polygenic Genetic Studies of Non-alcoholic Fatty Liver DiseaseR01DK131787 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$677k
Predictive models for incident cirrhosis in non-alcoholic fatty liver disease using genetic and electronic medical record-based risk factorsK08DK132312 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$165k
NIDDK NIH HHS K08 DK132312NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK106621NIDDK NIH HHS R01 DK107904NIDDK NIH HHS R01 DK128871NIDDK NIH HHS R01 DK131787
6 · The paper itself

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by increased hepatic steatosis with cardiometabolic disease and is a leading cause of advanced liver disease. We review here the genetic basis of MASLD. The genetic variants most consistently associated with hepatic steatosis implicate genes involved in lipoprotein input or output, glucose metabolism, adiposity/fat distribution, insulin resistance, or mitochondrial/ER biology. The distinct mechanisms by which these variants promote hepatic steatosis result in distinct effects on cardiometabolic disease that may be best suited to precision medicine. Recent work on gene-environment interactions has shown that genetic risk is not fixed and may be exacerbated or attenuated by modifiable (diet, exercise, alcohol intake) and nonmodifiable environmental risk factors. Some steatosis-associated variants, notably those in patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2), are associated with risk of developing adverse liver-related outcomes and provide information beyond clinical risk stratification tools, especially in individuals at intermediate to high risk for disease. Future work to better characterize disease heterogeneity by combining genetics with clinical risk factors to holistically predict risk and develop therapies based on genetic risk is required.

Indexed as

Fatty LiverGene-Environment InteractionGenetic VariationMembrane ProteinsPrecision MedicineAcyltransferasesHumansInsulin ResistanceLipasePhospholipases A2, Calcium-IndependentAcyltransferasesLipaseMembrane ProteinsPhospholipases A2, Calcium-IndependentPNPLA3 protein, humanTM6SF2 protein, human

Identifiers

PMID40166930
PMCPMC11957700

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.