SynthesisPLoS genetics2014
Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.
Open access · goldAbstract readMeta-Analysis
In one paragraph
Synthesis in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 5 pooled it
13.7field-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
88 citing papers in PubMed, 5 syntheses or guidelines pooled it, 214 citations in OpenAlex.
- Multi-ancestry genome-wide association analyses provide insights into the genetic basis of Hashimoto's thyroiditis.Nature genetics · 2026Pooled it
- An Intronic HCP5 Variant Is Associated With Age of Onset and Susceptibility to Graves Disease in UK and Polish Cohorts.The Journal of clinical endocrinology and metabolism · 2020Pooled it
- Effect of antithyroid antibodies on women with recurrent miscarriage: A meta-analysis.American journal of reproductive immunology (New York, N.Y. : 1989) · 2020Pooled it
- Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.Nature communications · 2018Pooled it
- Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus.Nature genetics · 2016Pooled it
- Familial associations between ANCA-associated vasculitis and other immune-mediated inflammatory diseases: a case control study.Rheumatology international · 2026Article
- Article
- Unraveling the underlying causality: a two-sample Mendelian randomization analysis of the association between thyroid function and gestational diabetes mellitus.Archives of medical science : AMS · 2026Article
- Public Cohort Analysis Identifies Thyroglobulin Variants as Hypothyroidism Risk Factors.bioRxiv : the preprint server for biology · 2025Article
- Thyroid peroxidase gene variants and autoimmunity in subclinical hypothyroidism: molecular mechanisms and clinical implications.Molecular biology reports · 2025Review
- Independent Effects of Hypothyroidism and Obesity on Endometrial Cancer Risk Revealed by Mendelian Randomisation.Biomedicines · 2025Article
- An Atlas of Genetic Correlations Between Thyroid Hormone Levels and Human Health-Related Traits.Health science reports · 2025Article
- Exon 11 Polymorphism (rs1126797) in the Thyroid Peroxidase (International journal of molecular sciences · 2025Article
- Identification ofCells · 2024Article
- Genome-wide association studies of thyroid-related hormones, dysfunction, and autoimmunity among 85,421 Chinese pregnancies.Nature communications · 2024Article
- LncRNAs are involved in regulating ageing and age-related disease through the adenosine monophosphate-activated protein kinase signalling pathway.Genes & diseases · 2024Review
- Review
- Is There a Link between Thyroid Peroxidase Gene Promoter Polymorphisms and Autoimmune Thyroiditis in the Polish Population?International journal of molecular sciences · 2024Article
- The Potential Coexistence of Autoimmune Thyroid Diseases and Pediatric VulvarChildren (Basel, Switzerland) · 2024Article
- Casual associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines.Frontiers in endocrinology · 2024Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
118 authors at 20 institutions in 10 countries.
Marco MediciDepartment of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Eleonora PorcuIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy ; Dipartimento di Scienze Biomediche, Universita di Sassari, Sassari, Italy.
Giorgio PistisDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
Alexander TeumerInterfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
Suzanne J BrownDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Richard A JensenCardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington, United States of America.
Rajesh RawalInstitute for Genetic Epidemiology, Helmholtz Zentrum Munich, Munich/Neuherberg, Germany.
Greet L RoefDepartment of Endocrinology and Internal Medicine, University Hospital Ghent and Faculty of Medicine, Ghent University, Ghent, Belgium.
Theo S PlantingaInternal Medicine, Division of Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Sita H VermeulenDepartment for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands.
Jari LahtiInstitute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Matthew J SimmondsOxford Centre for Diabetes, Endocrinology and Metabolism and NIHR Oxford Biomedical Research Centre, Oxford, UK Churchill Hospital, Headington, Oxford, United Kingdom.
Lise Lotte N HusemoenResearch Centre for Prevention and Health, Glostrup University Hospital, the Capital Region of Denmark, Glostrup, Denmark.
Rachel M FreathyGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
Beverley M ShieldsPeninsula NIHR Clinical Research Facility, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
Diana PietznerInstitute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Rebecca NagyComprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
Linda BroerDepartment of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Layal ChakerDepartment of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Tim I M KorevaarDepartment of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Maria Grazia PliaIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
Cinzia SalaDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
Uwe VölkerInterfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
J Brent RichardsDepartments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, McGill University, Montreal, Canada ; Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Fred C SweepDepartment for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands.
Christian GiegerInstitute for Genetic Epidemiology, Helmholtz Zentrum Munich, Munich/Neuherberg, Germany.
Tanguy CorreDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
Eero KajantieNational Institute for Health and Welfare, Helsinki, Finland ; Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
Betina ThuesenResearch Centre for Prevention and Health, Glostrup University Hospital, the Capital Region of Denmark, Glostrup, Denmark.
Youri E TaesDepartment of Endocrinology and Internal Medicine, University Hospital Ghent and Faculty of Medicine, Ghent University, Ghent, Belgium.
W Edward VisserDepartment of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Andrew T HattersleyPeninsula NIHR Clinical Research Facility, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
Jürgen KratzschInstitute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
Alexander HamiltonOxford Centre for Diabetes, Endocrinology and Metabolism and NIHR Oxford Biomedical Research Centre, Oxford, UK Churchill Hospital, Headington, Oxford, United Kingdom.
Wei LiComprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
Georg HomuthInterfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
Monia LobinaIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
Stefano MariottiDipartimento di Scienze Biomediche, Universita di Sassari, Sassari, Italy.
Nicole SoranzoWellcome Trust Sanger Institute, Hixton, United Kingdom.
Massimiliano CoccaDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
Matthias NauckInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Christin SpielhagenInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Alec RossDepartment for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands.
Alice ArnoldDepartment of Biostatistics, University of Washington, Seattle, Washington, United States of America.
Martijn van de BuntOxford Centre for Diabetes, Endocrinology and Metabolism and NIHR Oxford Biomedical Research Centre, Oxford, UK Churchill Hospital, Headington, Oxford, United Kingdom.
Sandya LiyanarachchiComprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
Margit HeierHelmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany.
Hans Jörgen GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS Hospital Stralsund, Greifswald, Germany.
Corrado MasciulloDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
Tessel E GaleslootDepartment for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands.
Ee M LimPathwest Laboratory Medicine WA, Nedlands, Western Australia, Australia.
Eva ReischlResearch Unit of Molecular Epidemiology Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Peter J LeedmanSchool of Medicine and Pharmacology, the University of Western Australia, Crawley, Western Australia, Australia ; UWA Centre for Medical Research, Western Australian Institute for Medical Research, Perth, Western Australia, Australia.
Sandra LaiIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
Alessandro DelitalaDipartimento di Scienze Biomediche, Universita di Sassari, Sassari, Italy.
Alexandra P BremnerSchool of Population Health, University of Western Australia, Nedlands, Western Australia, Australia.
David I W PhilipsMRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom.
John P BeilbyPathwest Laboratory Medicine WA, Nedlands, Western Australia, Australia ; School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
Antonella MulasIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
Matteo VocaleHigh Performance Computing and Network, CRS4, Parco Tecnologico della Sardegna, Pula, Italy.
Goncalo AbecasisCenter for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America.
Tom ForsenDepartment of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland ; Vaasa Health Care Centre, Diabetes Unit, Vaasa, Finland.
Alan JamesSchool of Medicine and Pharmacology, the University of Western Australia, Crawley, Western Australia, Australia ; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Elisabeth WidenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Jennie HuiPathwest Laboratory Medicine WA, Nedlands, Western Australia, Australia.
Holger ProkischInstitute of Human Genetics, Helmholtz Zentrum Munich, Munich, Germany ; Institute of Human Genetics, Technische Universität München, Munich, Germany.
Ernst E RietzschelDepartment of Cardiology and Internal Medicine, University Hospital Ghent and Faculty of Medicine, Ghent University, Ghent, Belgium.
Aarno PalotieInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom ; Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
Peter FeddemaDiagnostica Stago, Doncaster, Victoria, Australia.
Stephen J FletcherPathwest Laboratory Medicine WA, Nedlands, Western Australia, Australia.
Katharina SchrammInstitute of Human Genetics, Helmholtz Zentrum Munich, Munich, Germany.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, California, United States of America ; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, United States of America.
Alexander KluttigInstitute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Dörte RadkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Michela TragliaDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
Gabriela L SurdulescuDepartment of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Huiling HeComprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
Jayne A FranklynSchool of Clinical and Experimental Medicine, College of Medical and Dental Sciences, Univeristy of Birmingham, Edgbaston, Birmingham, United Kingdom.
Daniel TillerInstitute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Bijay VaidyaDiabetes, Endocrinology and Vascular Health Centre, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom.
Tim de MeyerBIOBIX Lab. for Bioinformatics and Computational Genomics, Dept. of Mathematical Modelling, Statistics and Bioinformatics. Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
Torben JørgensenResearch Centre for Prevention and Health, Glostrup University Hospital, the Capital Region of Denmark, Glostrup, Denmark ; Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
Johan G ErikssonNational Institute for Health and Welfare, Helsinki, Finland ; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland ; Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland ; Folkhalsan Research Centre, Helsinki, Finland ; Vasa Central Hospital, Vasa, Finland.
Peter C O'LearySchool of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia ; Curtin Health Innovation Research Institute, Curtin University of Technology, Bentley, Western Australia, Australia.
Eric WichmannInstitute of Epidemiology I, Helmholtz Zentrum Munich, Munich, Germany.
Ad R HermusInternal Medicine, Division of Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington, United States of America ; Group Health Research Institute, Group Health Cooperative, Seattle, Washington, United States of America.
Till IttermannInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Albert HofmanDepartment of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Emanuele BosiDepartment of Internal Medicine, Diabetes & Endocrinology Unit, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy.
David SchlessingerLaboratory of Genetics, National Institute on Aging, Baltimore, Maryland, United States of America.
Henri WallaschofskiInstitute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
Nicola PirastuInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy ; University of Trieste, Trieste, Italy.
Yurii S AulchenkoDepartment of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Albert de la ChapelleComprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
Romana T Netea-MaierInternal Medicine, Division of Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Stephen C L GoughOxford Centre for Diabetes, Endocrinology and Metabolism and NIHR Oxford Biomedical Research Centre, Oxford, UK Churchill Hospital, Headington, Oxford, United Kingdom.
Henriette Meyer Zu SchwabedissenBiopharmacy, Department of Pharmaceutical Sciences, University Basel, Basel, Switzerland.
Timothy M FraylingGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
Jean-Marc KaufmanDepartment of Endocrinology and Internal Medicine, University Hospital Ghent and Faculty of Medicine, Ghent University, Ghent, Belgium.
Allan LinnebergResearch Centre for Prevention and Health, Glostrup University Hospital, the Capital Region of Denmark, Glostrup, Denmark.
Katri RäikkönenInstitute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Johannes W A SmitInternal Medicine, Division of Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Lambertus A KiemeneyDepartment for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands.
Fernando RivadeneiraDepartment of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands ; Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands ; Netherlands Consortium for Healthy Aging, Netherlands Genomics Initiative, Leiden, The Netherlands.
André G UitterlindenDepartment of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands ; Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands ; Netherlands Consortium for Healthy Aging, Netherlands Genomics Initiative, Leiden, The Netherlands.
John P WalshDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia ; School of Medicine and Pharmacology, the University of Western Australia, Crawley, Western Australia, Australia.
Christa MeisingerHelmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany.
Martin den HeijerDepartment of Internal Medicine, VU Medical Center, Amsterdam, The Netherlands.
Theo J VisserDepartment of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Timothy D SpectorDepartment of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Scott G WilsonDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia ; School of Medicine and Pharmacology, the University of Western Australia, Crawley, Western Australia, Australia ; Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Anne CappolaDivision of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Daniela TonioloDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy ; Institute of Molecular Genetics-CNR, Pavia, Italy.
Serena SannaIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
Silvia NaitzaIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
Robin P PeetersDepartment of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Erasmus MC · NLHelmholtz Zentrum München · DEInstitute of Genetic and Biomedical Research · ITRadboud University Nijmegen · NLUniversitätsmedizin Greifswald · DEThe Ohio State University · USGhent University Hospital · BEPathwest Laboratory Medicine · AUUniversity of Helsinki · FIChurchill Hospital · GBGlostrup Hospital · DKKing's College London · GBMartin Luther University Halle-Wittenberg · DERadboud University Medical Center · NLSir Charles Gairdner Hospital · AUUniversität Greifswald · DEUniversity of Exeter · GBUniversity of Washington · USFinnish Institute for Health and Welfare · FINetherlands Consortium for Healthy Ageing · NL
Funding
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MSelective Modulation of Thyroidal RadioiodineP01CA124570 · NCI · OHIO STATE UNIVERSITY · PI RINGEL, MATTHEW D · 2008 to 2017
$23.4MUCLA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033176 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2011 to 2011
$15.5MExceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MCHS Events Follow-up StudyR01HL080295 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2009 to 2014
$6.3MWGA Study to Identify Genetic Variants Associated with CV Events in CHSR01HL087652 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2007 to 2009
$5.1MCHS Events Follow-up StudyU01HL080295 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2005 to 2008
$4.6MComputational and Statistical Models for Human PedigreesR01HG002651 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2003 to 2008
$2.9MExceptional Survival: Trajectories to Functional Aging (CHS All Stars)R56AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2010 to 2010
$300kNCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCI NIH HHS P01 CA124570NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA16058NCRR NIH HHS UL1 RR033176NCRR NIH HHS UL1RR033176NHGRI NIH HHS R01 HG002651NHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HL080295NHLBI NIH HHS HL087652NHLBI NIH HHS HL105756NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL105756NHLBI NIH HHS U01 HL080295NIA NIH HHS AG023629NIA NIH HHS R01 AG023629NIA NIH HHS R56 AG023629NIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK063491Wellcome TrustWellcome Trust 085541/Z/08/ZWellcome Trust WT089062
Abstract
Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10(-8)) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68-2.81, P = 8.1×10(-8)), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26-1.82, P = 2.9×10(-6)), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66-0.89, P = 6.5×10(-4)). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22-1.54, P = 1.2×10(-7) and OR: 1.25, 95% CI 1.12-1.39, P = 6.2×10(-5)). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18-2.10, P = 1.9×10(-3)). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction.
Indexed as
AutoantibodiesGenetic LociGenome-Wide Association StudyGraves DiseaseHashimoto DiseaseHumansIodide PeroxidaseRisk FactorsThyroiditis, AutoimmuneThyrotropinAutoantibodiesIodide Peroxidasethyroid microsomal antibodiesThyrotropin
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