Discovery meta-analyses included data from 22 independent cohorts with 54,288 subjects for the TSH analyses, and from 19 cohorts with 49,269 subjects for FT4, 53,423 subjects (3440 cases) for hypothyroidism, and 51,823 subjects (1840 cases) for hyperthyroidism (Supplementary Data 1). Selected SNPs from the TSH or FT4 analyses were carried forward for replication with in silico GWAS data from 5 cohorts (9053 subjects) and de novo genotyping in additional 5 cohorts (13,330 subjects). All subjects gave informed consent and studies were approved by the cohort-specific ethics committees. We used the results of the GWAS of TPOAb positivity that included 18,297 subjects20 (link) for a look-up of all the 53 TSH-associated loci or their HapMapII proxies (r² > 0.8 in a 1 Mb window) that were available in that dataset to assess their relation to autoimmune hypothyroidism. A complementary look-up was performed for the 52 SNPs that were available in a GWAS on Graves’ disease diagnosed by clinical examinations, circulating thyroid hormone and TSH concentrations, serum levels of antibodies against thyroglobulin, thyroid microsomes, and TSH receptors, ultrasonography, [99m]TCO4− (technetium-99m pertechnetate) (or [123I] (radioactive iodine)) uptake and thyroid scintigraphy using the data of the BioBank Japan Project (BBJ) including 1747 patients and 6420 controls (Supplementary Data 1).
Teumer A., Chaker L., Groeneweg S., Li Y., Di Munno C., Barbieri C., Schultheiss U.T., Traglia M., Ahluwalia T.S., Akiyama M., Appel E.V., Arking D.E., Arnold A., Astrup A., Beekman M., Beilby J.P., Bekaert S., Boerwinkle E., Brown S.J., De Buyzere M., Campbell P.J., Ceresini G., Cerqueira C., Cucca F., Deary I.J., Deelen J., Eckardt K.U., Ekici A.B., Eriksson J.G., Ferrrucci L., Fiers T., Fiorillo E., Ford I., Fox C.S., Fuchsberger C., Galesloot T.E., Gieger C., Gögele M., De Grandi A., Grarup N., Greiser K.H., Haljas K., Hansen T., Harris S.E., van Heemst D., den Heijer M., Hicks A.A., den Hollander W., Homuth G., Hui J., Ikram M.A., Ittermann T., Jensen R.A., Jing J., Jukema J.W., Kajantie E., Kamatani Y., Kasbohm E., Kaufman J.M., Kiemeney L.A., Kloppenburg M., Kronenberg F., Kubo M., Lahti J., Lapauw B., Li S., Liewald D.C., Lim E.M., Linneberg A., Marina M., Mascalzoni D., Matsuda K., Medenwald D., Meisinger C., Meulenbelt I., De Meyer T., Meyer zu Schwabedissen H.E., Mikolajczyk R., Moed M., Netea-Maier R.T., Nolte I.M., Okada Y., Pala M., Pattaro C., Pedersen O., Petersmann A., Porcu E., Postmus I., Pramstaller P.P., Psaty B.M., Ramos Y.F., Rawal R., Redmond P., Richards J.B., Rietzschel E.R., Rivadeneira F., Roef G., Rotter J.I., Sala C.F., Schlessinger D., Selvin E., Slagboom P.E., Soranzo N., Sørensen T.I., Spector T.D., Starr J.M., Stott D.J., Taes Y., Taliun D., Tanaka T., Thuesen B., Tiller D., Toniolo D., Uitterlinden A.G., Visser W.E., Walsh J.P., Wilson S.G., Wolffenbuttel B.H., Yang Q., Zheng H.F., Cappola A., Peeters R.P., Naitza S., Völzke H., Sanna S., Köttgen A., Visser T.J, & Medici M. (2018). Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nature Communications, 9, 4455.
Corresponding Organization : German Centre for Cardiovascular Research
Other organizations :
Erasmus MC, University of Freiburg, University of Sannio, Steno Diabetes Center, Novo Nordisk Foundation, University of Copenhagen, RIKEN Center for Integrative Medical Sciences, Johns Hopkins Medicine, Johns Hopkins University, University of Washington, Seattle University, Leiden University Medical Center, Pathwest Laboratory Medicine, University of Western Australia, Ghent University Hospital, The University of Texas Health Science Center at Houston, Sir Charles Gairdner Hospital, University of Parma, Center for Clinical Research and Prevention, Frederiksberg Hospital, Institute of Genetic and Biomedical Research, University of Sassari, University of Edinburgh, Max Planck Institute for Biology of Ageing, Friedrich-Alexander-Universität Erlangen-Nürnberg, Charité - Universitätsmedizin Berlin, University of Helsinki, Helsinki University Hospital, Folkhälsans Forskningscentrum, Finnish Institute for Health and Welfare, National Institute on Aging, University of Glasgow, Framingham Heart Study, National Heart Lung and Blood Institute, Brigham and Women's Hospital, Harvard University, Institute for Biomedicine, Eurac Research, Radboud University Nijmegen, Radboud University Medical Center, Helmholtz Zentrum München, German Cancer Research Center, MRC Institute of Genetics and Molecular Medicine, Vrije Universiteit Amsterdam, Oulu University Hospital, University of Oulu, Kyoto University, Friedrich-Loeffler-Institut, Innsbruck Medical University, Universität Innsbruck, Boston University, Rigshospitalet, The University of Tokyo, Martin Luther University Halle-Wittenberg, University of Augsburg, Ludwig-Maximilians-Universität München, Ghent University, University of Basel, University Medical Center Groningen, University of Groningen, Osaka University, SIB Swiss Institute of Bioinformatics, University of Lausanne, Kaiser Permanente Washington Health Research Institute, Jewish General Hospital, King's College London, The Lundquist Institute, UCLA Medical Center, Harbor–UCLA Medical Center, Institute on Aging, National Institutes of Health, Wellcome Sanger Institute, Alzheimer Scotland, AZ Sint-Jan, Westlake University, Affiliated Hospital of Hangzhou Normal University, University of Pennsylvania
All subjects gave informed consent and studies were approved by the cohort-specific ethics committees.
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