Evidence map›Paper›PMID 21423719›Full record

SynthesisPLoS genetics2011

Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

Elizabeth K Speliotes, Laura M Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J Kim, Cameron D Palmer, Vilmundur Gudnason, Gudny Eiriksdottir, Melissa E Garcia, Lenore J Launer and 28 more

Registry-linked trialOpen access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03783195 (Genetic-specific Effects of Fructose on Liver Lipogenesis), which is not on this map. Cited by 546 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
546citing papers in PubMed, 7 pooled it
40.5field-weighted citation impact, top 1% 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.

NCT03783195 nacompletednot on this mapstarted 2019, after this paper: background citation

Genetic-specific Effects of Fructose on Liver Lipogenesis

TypeinterventionalSponsorUniversity of North Carolina, Chapel HillRan2019 to 2023Enrolled15ConditionsNAFLDArmsSugar drink
3 · Its place in the literature

Who cites it

546 citing papers in PubMed, 7 syntheses or guidelines pooled it, 993 citations in OpenAlex.

  1. Pooled it
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  11. Age-Specific Associations of Polygenic Risk Scores With Advanced Fibrosis and Histological Activity in Biopsy-Proven MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
  12. Review
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486 more citing papers are in PubMed but not listed here.

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

38 authors at 16 institutions in 3 countries.

Elizabeth K SpeliotesDepartment of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, United States of America. espeliot@med.umich.edu
Laura M Yerges-Armstrong
Jun Wu
Ruben Hernaez
Lauren J Kim
Cameron D Palmer
Vilmundur Gudnason
Gudny Eiriksdottir
Melissa E Garcia
Lenore J Launer
Michael A Nalls
Jeanne M Clark
Braxton D Mitchell
Alan R Shuldiner
Johannah L Butler
Marta Tomas
Udo Hoffmann
Shih-Jen Hwang
Joseph M Massaro
Christopher J O'Donnell
Dushyant V Sahani
Veikko Salomaa
Eric E Schadt
Stephen M Schwartz
David S Siscovick
NASH CRN
GIANT Consortium
MAGIC Investigators
Benjamin F Voight
J Jeffrey Carr
Mary F Feitosa
Tamara B Harris
Caroline S Fox
Albert V Smith
W H Linda Kao
Joel N Hirschhorn
Ingrid B Borecki
GOLD Consortium
National Institutes of Health · USBroad Institute · USJohns Hopkins University · USMassachusetts General Hospital · USUniversity of Maryland, Baltimore · USWashington University in St. Louis · USBoston Children's Hospital · USUniversity of Washington · USBoston University · USIcelandic Heart Association · ISMedStar Washington Hospital Center · USMunicipal Institute for Medical Research · ESNational Heart Lung and Blood Institute · USPacific Biosciences (United States) · USUniversity of Iceland · ISWake Forest University · US

Funding

ZOVIRAX CREAM TO TREAT HERPES LABIALIS IN ADOLESCENTSM01RR000827 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHANG, R JEFFREY · 1985 to 2010
$74.3M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024989 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2007 to 2011
$53.7M
Genetic analysis of type II diabetes in Finnish populationZIAHG000024 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ERDOS, MICHAEL · 2009 to 2025
$38.2M
ZOLENDRONIC ACID IN CHILDREN W/ SEVERE OSTEOGENESIS IMPERFECTAM01RR000188 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI SHEARER, WILLIAM THOMAS · 1985 to 2011
$30.6M
ZOSUQUIDAR TRIHYDROCHLORIDE DURING CONVENTIONAL INDUCTION AND POST-REMISSIONM01RR000750 · NCRR · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI RODRIGUEZ, HENRY · 1985 to 2008
$25.5M
X-LINKED HYPOPHOSPHATEMIAM01RR000065 · NCRR · VIRGINIA COMMONWEALTH UNIVERSITY · PI SANYAL, ARUN J · 1985 to 2010
$24.8M
Pediatric Trials in Non-Alcoholic Steatohepatitis (NASH)U01DK061734 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROHIT LOOMBA · 2002 to 2026
$24.4M
Continuation of the Non-Alcoholic Steatohepatitis Clinical Research Network (NASHU01DK061730 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI TONASCIA, JAMES A · 2002 to 2018
$23.2M
Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
RESEARCH TRAINING IN DIGESTIVE DISEASES AND NUTRITIONT32DK007191 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1986 to 2026
$14.6M
ZAP-70 EXPRESSION, CD38 EXPRESSION AND PROGNOSIS IN CHRONIC LYMPHOCYTIC LEUKEMIAM01RR020359 · NCRR · CHILDREN'S RESEARCH INSTITUTE · PI HINDS, PAMELA S · 2005 to 2010
$13.8M
Cell Interactions in the Inflamed Intestinal MucosaR01DK075787 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI JOEL N HIRSCHHORN · 2007 to 2026
$13.1M
British Heart Foundation PG/09/002/26056British Heart Foundation RG/07/008/23674Intramural NIH HHSMedical Research Council G0100222Medical Research Council G0401527Medical Research Council G0701863Medical Research Council G0801056Medical Research Council G0902037Medical Research Council G1000143Medical Research Council G1000758Medical Research Council G19/35Medical Research Council G8802774Medical Research Council MC_U106179471Medical Research Council MC_U127561128Medical Research Council MC_UP_A100_1003Medical Research Council MC_UP_A620_1014Medical Research Council MC_UP_A620_1015NCRR NIH HHS M01 RR000065NCRR NIH HHS M01RR000065NCRR NIH HHS M01 RR000188NCRR NIH HHS M01 RR000750NCRR NIH HHS M01RR000750NCRR NIH HHS M01 RR000827NCRR NIH HHS M01RR000827NCRR NIH HHS M01RR00188NCRR NIH HHS M01 RR020359NCRR NIH HHS M01RR020359NCRR NIH HHS UL1 RR024989NCRR NIH HHS UL1RR024989NCRR NIH HHS UL1RR02501401NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS N02-HL-6-4278NHLBI NIH HHS R01 HL087700NHLBI NIH HHS R01HL087700NHLBI NIH HHS R01 HL088119NHLBI NIH HHS R01HL088119NHLBI NIH HHS U01 HL072515NHLBI NIH HHS U01 HL084756NHLBI NIH HHS U01 HL72515NIAMS NIH HHS F32 AR059469NIAMS NIH HHS F32AR059469NIA NIH HHS N01 AG012100NIA NIH HHS R01 AG018728NIA NIH HHS R01 AG18728NIA NIH HHS T32 AG000262NIA NIH HHS T32AG000262NIDDK NIH HHS F32 DK079466NIDDK NIH HHS F32 DK079466-01NIDDK NIH HHS K01 DK067207NIDDK NIH HHS K23 DK080145NIDDK NIH HHS K23DK080145-01NIDDK NIH HHS K24 DK002957NIDDK NIH HHS P30 DK072488NIDDK NIH HHS P30DK072488NIDDK NIH HHS P60 DK079637NIDDK NIH HHS R01 DK075681NIDDK NIH HHS R01DK075681NIDDK NIH HHS R01 DK075787NIDDK NIH HHS R01DK075787NIDDK NIH HHS T32 DK007191NIDDK NIH HHS T32 DK07191-32NIDDK NIH HHS U01 DK061713NIDDK NIH HHS U01DK061713NIDDK NIH HHS U01 DK061718NIDDK NIH HHS U01DK061718NIDDK NIH HHS U01 DK061728NIDDK NIH HHS U01DK061728NIDDK NIH HHS U01 DK061730NIDDK NIH HHS U01DK061730NIDDK NIH HHS U01 DK061731NIDDK NIH HHS U01DK061731NIDDK NIH HHS U01 DK061732NIDDK NIH HHS U01DK061732NIDDK NIH HHS U01 DK061734NIDDK NIH HHS U01DK061734NIDDK NIH HHS U01 DK061737NIDDK NIH HHS U01DK061737NIDDK NIH HHS U01 DK061738NIDDK NIH HHS U01DK061738PHS HHS ULRR02413101Wellcome Trust 090532Wellcome Trust 095515
6 · The paper itself

Abstract

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.

Indexed as

AcyltransferasesAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overBlood GlucoseCase-Control StudiesChondroitin Sulfate ProteoglycansCohort StudiesFatty LiverGenome-Wide Association StudyHumansInsulinLectins, C-TypeLipaseMaleAcyltransferasesAdaptor Proteins, Signal TransducingBlood GlucoseChondroitin Sulfate ProteoglycansGCKR protein, humanInsulinLectins, C-TypeLipaseMembrane ProteinsNCAN protein, humanNerve Tissue ProteinsNeurocanPhospholipases A2, Calcium-IndependentPNPLA3 protein, human

Identifiers

PMID21423719
PMCPMC3053321
OpenAlexW2156760391

What OpenQuestion holds

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Registered trials

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 OpenQuestion graph.