GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer

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dc.contributor.author Zhou, Wei
dc.contributor.author Brumpton, Ben
dc.contributor.author Kabil, Omer
dc.contributor.author Gudmundsson, Julius
dc.contributor.author Thorleifsson, Gudmar
dc.contributor.author Weinstock, Josh
dc.contributor.author Zawistowski, Matthew
dc.contributor.author Nielsen, Jonas B.
dc.contributor.author Chaker, Layal
dc.contributor.author Medici, Marco
dc.contributor.author Teumer, Alexander
dc.contributor.author Naitza, Silvia
dc.contributor.author Sanna, Serena
dc.contributor.author Schultheiss, Ulla T.
dc.contributor.author Cappola, Anne
dc.contributor.author Karjalainen, Juha
dc.contributor.author Kurki, Mitja
dc.contributor.author Oneka, Morgan
dc.contributor.author Taylor, Peter
dc.contributor.author Fritsche, Lars G.
dc.contributor.author Graham, Sarah E.
dc.contributor.author Wolford, Brooke N.
dc.contributor.author Overton, William
dc.contributor.author Rasheed, Humaira
dc.contributor.author Haug, Eirin B.
dc.contributor.author Gabrielsen, Maiken E.
dc.contributor.author Skogholt, Anne Heidi
dc.contributor.author Surakka, Ida
dc.contributor.author Smith, George Davey
dc.contributor.author Pandit, Anita
dc.contributor.author Roychowdhury, Tanmoy
dc.contributor.author Hornsby, Whitney E.
dc.contributor.author Jonasson, Jon G.
dc.contributor.author Senter, Leigha
dc.contributor.author Liyanarachchi, Sandya
dc.contributor.author Ringel, Matthew D.
dc.contributor.author Xu, Li
dc.contributor.author Kiemeney, Lambertus A.
dc.contributor.author He, Huiling
dc.contributor.author Netea-Maier, Romana T.
dc.contributor.author Mayordomo, Jose
dc.contributor.author Plantinga, Theo S.
dc.contributor.author Hrafnkelsson, Jon
dc.contributor.author Hjartarson, Hannes
dc.contributor.author Sturgis, Erich M.
dc.contributor.author Palotie, Aarno
dc.contributor.author Daly, Mark
dc.contributor.author Citterio, Cintia E.
dc.contributor.author Arvan, Peter
dc.contributor.author Brummett, Chad M.
dc.contributor.author Boehnke, Michael
dc.contributor.author de la Chapelle, Albert
dc.contributor.author Stefansson, Kari
dc.contributor.author Hveem, Kristian
dc.contributor.author Willer, Cristen J.
dc.contributor.author Asvold, Bjorn Olav
dc.date.accessioned 2020-09-17T05:02:01Z
dc.date.available 2020-09-17T05:02:01Z
dc.date.issued 2020-08-07
dc.identifier.citation Zhou , W , Brumpton , B , Kabil , O , Gudmundsson , J , Thorleifsson , G , Weinstock , J , Zawistowski , M , Nielsen , J B , Chaker , L , Medici , M , Teumer , A , Naitza , S , Sanna , S , Schultheiss , U T , Cappola , A , Karjalainen , J , Kurki , M , Oneka , M , Taylor , P , Fritsche , L G , Graham , S E , Wolford , B N , Overton , W , Rasheed , H , Haug , E B , Gabrielsen , M E , Skogholt , A H , Surakka , I , Smith , G D , Pandit , A , Roychowdhury , T , Hornsby , W E , Jonasson , J G , Senter , L , Liyanarachchi , S , Ringel , M D , Xu , L , Kiemeney , L A , He , H , Netea-Maier , R T , Mayordomo , J , Plantinga , T S , Hrafnkelsson , J , Hjartarson , H , Sturgis , E M , Palotie , A , Daly , M , Citterio , C E , Arvan , P , Brummett , C M , Boehnke , M , de la Chapelle , A , Stefansson , K , Hveem , K , Willer , C J & Asvold , B O 2020 , ' GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer ' , Nature Communications , vol. 11 , no. 1 , 3981 . https://doi.org/10.1038/s41467-020-17718-z
dc.identifier.other PURE: 144614731
dc.identifier.other PURE UUID: 70ff9846-1c09-4867-9953-282e79ce63c3
dc.identifier.other WOS: 000561098400034
dc.identifier.other ORCID: /0000-0002-2527-5874/work/97266465
dc.identifier.uri http://hdl.handle.net/10138/319425
dc.description Correction: Volume12, Issue1 Article Number7354 DOI10.1038/s41467-021-27675-w PublishedDEC 16 2021
dc.description.abstract Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors. Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. Here, the authors conduct a GWAS and suggest protective effect of higher TSH on risk of thyroid cancer and goitre. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof Nature Communications
dc.rights cc_by
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject ENDOGENOUS SUBCLINICAL HYPERTHYROIDISM
dc.subject SERUM THYROTROPIN CONCENTRATION
dc.subject GENOME-WIDE ASSOCIATION
dc.subject CONGENITAL HYPOTHYROIDISM
dc.subject COMMON VARIANTS
dc.subject TSH
dc.subject RECEPTOR
dc.subject THYROGLOBULIN
dc.subject HYPERTENSION
dc.subject MALIGNANCY
dc.subject 3111 Biomedicine
dc.title GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer en
dc.type Article
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.contributor.organization University of Helsinki
dc.contributor.organization Centre of Excellence in Complex Disease Genetics
dc.contributor.organization Research Programs Unit
dc.contributor.organization Aarno Palotie / Principal Investigator
dc.contributor.organization Genomics of Neurological and Neuropsychiatric Disorders
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41467-020-17718-z
dc.relation.issn 2041-1723
dc.rights.accesslevel openAccess
dc.type.version publishedVersion
dc.type.version publishedVersion

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