SynthesisGastroenterology2016
Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-Wide Association Studies.
Open access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in Gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 7 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 7 pooled it
11.0field-weighted citation impact, top 1% of its field
What it found
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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.
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.
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Who cites it
55 citing papers in PubMed, 7 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Estimating global prevalence of gallbladder stones in general population from 2000 to 2024: systematic review and meta-analysis.Annals of medicine · 2025Pooled it
- Integrative genome-wide analysis unveils the genetic landscape of gallstone disease and highlights novel loci with therapeutic potential.BMJ open gastroenterology · 2025Pooled it
- Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.Genome biology · 2022Pooled it
- GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.Nature communications · 2022Pooled it
- Causal effects of gallstone disease on risk of gastrointestinal cancer in Chinese.British journal of cancer · 2021Pooled it
- Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals.Communications biology · 2019Pooled it
- Genome-wide association meta-analysis yields 20 loci associated with gallstone disease.Nature communications · 2018Pooled it
- Multilevel genome-wide analysis reveals shared genetic architecture between acute pancreatitis and body fat distribution.World journal of emergency medicine · 2026Article
- Multi-cohort proteogenomic analyses reveal genetic effects across the proteome and diseasome.Cell · 2026Article
- Denture use is associated with a higher risk of cholelithiasis: a prospective cohort study.BMC oral health · 2026Article
- Aflatoxins and Human Health: Global Exposure, Disease Burden, and One Health Strategies.Toxins · 2026Review
- Asymptomatic gallstone disease: Re-evaluating the threshold for surgical options in the era of precision medicine.World journal of gastrointestinal surgery · 2025Review
- Novel Insights Into the Genetic Basis Between Cholelithiasis and Four Dietary Patterns.Food science & nutrition · 2025Article
- Let us maximize the clinical utility of genetic testing while unraveling the pathogenesis of gallstone disease.Internal and emergency medicine · 2025Article
- Genetics of Gallstones.Genes · 2025Review
- Hypothyroidism affects cholelithiasis causally: A two-sample bidirectional Mendelian randomization study.Journal of biomedical research · 2025Article
- Network Mendelian randomisation analysis deciphers protein pathways linking type 2 diabetes and gastrointestinal disease.Diabetes, obesity & metabolism · 2025Article
- The roles of lifestyle factors and genetic risk in the association between night shift work and cholelithiasis: a prospective cohort study.Frontiers in endocrinology · 2025Article
- Metabolomic profiles of incident gallstone disease.BMJ open gastroenterology · 2024Article
- [New Progress in Longitudinal Research on the Risk Factors for Cholelithiasis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
Corrections and comments
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Authors and funding
55 authors at 19 institutions in 5 countries.
Amit D JoshiProgram in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: ajoshi@hsph.harvard.edu.
Charlotte AnderssonThe National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts. Electronic address: ca@heart.dk.
Stephan BuchMedical Department 1, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
Stefan StenderDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Raymond NoordamDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Lu-Chen WengDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minnesota.
Peter E WeekeDepartment of Medicine, Vanderbilt University, Nashville, Tennessee; Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen, Denmark.
Paul L AuerJoseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Bernhard BoehmDepartment of Internal Medicine I, Ulm University Hospital, Ulm, Germany.
Constance ChenProgram in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts.
Hyon ChoiDivision of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts.
Gary CurhanChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Joshua C DennyDepartment of Medicine, Vanderbilt University, Nashville, Tennessee; Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee.
Immaculata De VivoProgram in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
John D EicherThe National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, Massachusetts.
David EllinghausInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Aaron R FolsomDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minnesota.
Charles FuchsChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Manish GalaDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Jeffrey HaesslerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Albert HofmanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Frank HuDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
David J HunterProgram in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
Harry L A JanssenDepartment of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands; Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, Canada.
Jae H KangChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Peter KraftProgram in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
Wolfgang KratzerDepartment of Internal Medicine I, Ulm University Hospital, Ulm, Germany.
Wolfgang LiebInstitute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Pamela L LutseyDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minnesota.
Sarwa Darwish MuradDepartment of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
Børge G NordestgaardThe Copenhagen General Population Study, Herlev Hospital, Herlev, Denmark; Department of Clinical Biochemistry, Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Louis R PasqualeChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
Alex P ReinerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Paul M RidkerDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Eric RimmChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
Lynda M RoseDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Christian M ShafferDepartment of Medicine, Vanderbilt University, Nashville, Tennessee.
Clemens SchafmayerDepartment of General, Abdominal, Thoracic and Transplantation Surgery, University of Kiel, Kiel, Germany.
Rulla M TamimiChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
André G UitterlindenDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Uwe VölkerDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; German Center for Cardiovascular Research, Greifswald, Germany; German Center for Diabetes Research, Greifswald, Germany.
Yoshiyuki WakabayashiNational Heart, Lung, and Blood Institute, DNA Sequencing Core Laboratory, Bethesda, Maryland.
Janey L WiggsDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
Jun ZhuNational Heart, Lung, and Blood Institute, DNA Sequencing Core Laboratory, Bethesda, Maryland.
Dan M RodenDepartment of Medicine, Vanderbilt University, Nashville, Tennessee.
Bruno H StrickerDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Weihong TangDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minnesota.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Jochen HampeMedical Department 1, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
Anne Tybjærg-HansenDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev Hospital, Herlev, Denmark.
Daniel I ChasmanDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Andrew T ChanDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: achan@mgh.harvard.edu.
Andrew D JohnsonThe National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, Massachusetts. Electronic address: johnsonad2@nhlbi.nih.gov.
Brigham and Women's Hospital · USErasmus MC · NLFred Hutch Cancer Center · USHarvard University · USUniversity of Minnesota · USVanderbilt University · USChristian-Albrechts-Universität zu Kiel · DENational Heart Lung and Blood Institute · USUniversitätsmedizin Greifswald · DEMassachusetts Department of Public Health · USNational Institutes of Health · USTechnische Universität Dresden · DEUniversity Hospital Ulm · DEHerlev Hospital · DKMassachusetts Eye and Ear Infirmary · USMassachusetts General Hospital · USRigshospitalet · DKUniversity Health Network · CAUniversity of Copenhagen · DK
Funding
Cardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3MDNA Sequencing Core (DSC)ZICHL006058 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ZHU, JUN · 2010 to 2016
$16.6MGene-Environment Interactions in GlaucomaR01EY015473 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI PASQUALE, LOUIS ROBERT · 2005 to 2021
$8.3MThe NEIGHBORHOOD: POAG Heritable Overall Operational DatabaseR01EY022305 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI WIGGS, JANEY L · 2012 to 2025
$7.9MVGER, the Vanderbilt Genome-Electronic Records ProjectU01HG008672 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DENNY, JOSHUA C., RODEN, DAN M · 2015 to 2019
$5.1MVanderbilt Genome Electronic Records ProjectU01HG006378 · NHGRI · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 2011 to 2014
$4.0MThe Women's Health Study: Infrastructure Support for Continued Cohort Follow-upUM1CA182913 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 2014 to 2018
$4.0MMentored Patient-Oriented Research in Digestive DiseasesK24DK098311 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHAN, ANDREW T · 2013 to 2017
$930kFHCRC High-Performance Computing ClusterS10OD020069 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KOOPERBERG, CHARLES L · 2015 to 2015
$600kIntramural NIH HHS Z99 HL999999NCI NIH HHS UM1 CA182913NEI NIH HHS R01 EY015473NEI NIH HHS R01 EY022305NHGRI NIH HHS U01 HG006378NHGRI NIH HHS U01 HG008672NIDDK NIH HHS K24 DK098311NIH HHS S10 OD020069
Abstract
BACKGROUND &
aimsA genome-wide association study (GWAS) of 280 cases identified the hepatic cholesterol transporter ABCG8 as a locus associated with risk for gallstone disease, but findings have not been reported from any other GWAS of this phenotype. We performed a large-scale, meta-analysis of GWASs of individuals of European ancestry with available prior genotype data, to identify additional genetic risk factors for gallstone disease.
methodsWe obtained per-allele odds ratio (OR) and standard error estimates using age- and sex-adjusted logistic regression models within each of the 10 discovery studies (8720 cases and 55,152 controls). We performed an inverse variance weighted, fixed-effects meta-analysis of study-specific estimates to identify single-nucleotide polymorphisms that were associated independently with gallstone disease. Associations were replicated in 6489 cases and 62,797 controls.
resultsWe observed independent associations for 2 single-nucleotide polymorphisms at the ABCG8 locus: rs11887534 (OR, 1.69; 95% confidence interval [CI], 1.54-1.86; P = 2.44 × 10(-60)) and rs4245791 (OR, 1.27; P = 1.90 × 10(-34)). We also identified and/or replicated associations for rs9843304 in TM4SF4 (OR, 1.12; 95% CI, 1.08-1.16; P = 6.09 × 10(-11)), rs2547231 in SULT2A1 (encodes a sulfoconjugation enzyme that acts on hydroxysteroids and cholesterol-derived sterol bile acids) (OR, 1.17; 95% CI, 1.12-1.21; P = 2.24 × 10(-10)), rs1260326 in glucokinase regulatory protein (OR, 1.12; 95% CI, 1.07-1.17; P = 2.55 × 10(-10)), and rs6471717 near CYP7A1 (encodes an enzyme that catalyzes conversion of cholesterol to primary bile acids) (OR, 1.11; 95% CI, 1.08-1.15; P = 8.84 × 10(-9)). Among individuals of African American and Hispanic American ancestry, rs11887534 and rs4245791 were associated positively with gallstone disease risk, whereas the association for the rs1260326 variant was inverse.
conclusionsIn this large-scale GWAS of gallstone disease, we identified 4 loci in genes that have putative functions in cholesterol metabolism and transport, and sulfonylation of bile acids or hydroxysteroids.
Indexed as
Genetic Predisposition to DiseaseAdultAgedATP Binding Cassette Transporter, Subfamily G, Member 8Black or African AmericanCase-Control StudiesCholesterolFemaleGallstonesGenetic LociGenome-Wide Association StudyHispanic or LatinoHumansLipid MetabolismLogistic ModelsMaleABCG8 protein, humanATP Binding Cassette Transporter, Subfamily G, Member 8CholesterolGeneticsGWASRisk FactorsSNP
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