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

Show simple item record Zhou, Wei Brumpton, Ben Kabil, Omer Gudmundsson, Julius Thorleifsson, Gudmar Weinstock, Josh Zawistowski, Matthew Nielsen, Jonas B. Chaker, Layal Medici, Marco Teumer, Alexander Naitza, Silvia Sanna, Serena Schultheiss, Ulla T. Cappola, Anne Karjalainen, Juha Kurki, Mitja Oneka, Morgan Taylor, Peter Fritsche, Lars G. Graham, Sarah E. Wolford, Brooke N. Overton, William Rasheed, Humaira Haug, Eirin B. Gabrielsen, Maiken E. Skogholt, Anne Heidi Surakka, Ida Smith, George Davey Pandit, Anita Roychowdhury, Tanmoy Hornsby, Whitney E. Jonasson, Jon G. Senter, Leigha Liyanarachchi, Sandya Ringel, Matthew D. Xu, Li Kiemeney, Lambertus A. He, Huiling Netea-Maier, Romana T. Mayordomo, Jose Plantinga, Theo S. Hrafnkelsson, Jon Hjartarson, Hannes Sturgis, Erich M. Palotie, Aarno Daly, Mark Citterio, Cintia E. Arvan, Peter Brummett, Chad M. Boehnke, Michael de la Chapelle, Albert Stefansson, Kari Hveem, Kristian Willer, Cristen J. Asvold, Bjorn Olav 2020-09-17T05:02:01Z 2020-09-17T05:02:01Z 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 .
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.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 TSH
dc.subject RECEPTOR
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.issn 2041-1723
dc.rights.accesslevel openAccess
dc.type.version publishedVersion
dc.type.version publishedVersion

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