Evidence mapPaperPMID 34184762Full record

ArticleGenetic epidemiology2021

Genome-wide association analysis of serum alanine and aspartate aminotransferase, and the modifying effects of BMI in 388k European individuals.

Chuan Gao, Anthony Marcketta, Joshua D Backman, Colm O'Dushlaine, Jeffrey Staples, Manuel Allen Revez Ferreira, Luca A Lotta, John D Overton, Jeffrey G Reid, Tooraj Mirshahi and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Genetic epidemiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
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

16 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Genetics of Metabolic Dysfunction-associated Steatotic Liver Disease: The State of the Art Update.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. The History of mARC.Molecules (Basel, Switzerland) · 2023
    Review
  12. Hepatocyte mARC1 promotes fatty liver disease.JHEP reports : innovation in hepatology · 2023
    Article
  13. Review
  14. International journal of molecular sciences · 2022
    Article
  15. Article
  16. 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

17 authors at 2 institutions in 1 country.

Chuan GaoRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.ORCID 0000-0002-4877-2072
Anthony MarckettaRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Joshua D BackmanRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Colm O'DushlaineRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Jeffrey StaplesRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Manuel Allen Revez FerreiraRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Luca A LottaRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
John D OvertonRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Jeffrey G ReidRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Tooraj MirshahiMolecular and Functional Genomics, Geisinger Clinic, Danville, Pennsylvania, USA.
Regeneron Genetics CenterRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Geisinger Regeneron Discovehr Collaboration
Aris BarasRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Gonçalo AbecasisRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Alan R ShuldinerRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Cristopher V Van HoutRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Shane McCarthyRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Regeneron (United States) · USGeisinger Medical Center · US

Funding

Medical Research Council MC_PC_17228Medical Research Council MC_QA137853
6 · The paper itself

Abstract

Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are biomarkers for liver health. Here we report the largest genome-wide association analysis to date of serum ALT and AST levels in over 388k people of European ancestry from UK biobank and DiscovEHR. Eleven million imputed markers with a minor allele frequency (MAF) ≥ 0.5% were analyzed. Overall, 300 ALT and 336 AST independent genome-wide significant associations were identified. Among them, 81 ALT and 61 AST associations are reported for the first time. Genome-wide interaction study identified 9 ALT and 12 AST independent associations significantly modified by body mass index (BMI), including several previously reported potential liver disease therapeutic targets, for example, PNPLA3, HSD17B13, and MARC1. While further work is necessary to understand the effect of ALT and AST-associated variants on liver disease, the weighted burden of significant BMI-modified signals is significantly associated with liver disease outcomes. In summary, this study identifies genetic associations which offer an important step forward in understanding the genetic architecture of serum ALT and AST levels. Significant interactions between BMI and genetic loci not only highlight the important role of adiposity in liver damage but also shed light on the genetic etiology of liver disease in obese individuals.

Indexed as

Body Mass IndexGenome-Wide Association StudyAlanine TransaminaseAspartate AminotransferasesHumansAlanine TransaminaseAspartate AminotransferasesALTASTGWASinteractionliver disease

Identifiers

PMID34184762
PMCPMC8457092
OpenAlexW3175493905

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.