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Whole-genome sequence-based analysis of thyroid function

Author

Listed:
  • Peter N. Taylor

    (Thyroid Research Group, Institute of Molecular & Experimental Medicine, Cardiff University School of Medicine, Cardiff University)

  • Eleonora Porcu

    (Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato
    Università di Sassari
    Center for Statistical Genetics, University of Michigan)

  • Shelby Chew

    (Sir Charles Gairdner Hospital)

  • Purdey J. Campbell

    (Sir Charles Gairdner Hospital)

  • Michela Traglia

    (San Raffaele Research Institute)

  • Suzanne J. Brown

    (Sir Charles Gairdner Hospital)

  • Benjamin H. Mullin

    (Sir Charles Gairdner Hospital
    School of Medicine and Pharmacology, University of Western Australia)

  • Hashem A. Shihab

    (MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove)

  • Josine Min

    (MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove)

  • Klaudia Walter

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Yasin Memari

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Jie Huang

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Michael R. Barnes

    (William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • John P. Beilby

    (Pathwest Laboratory Medicine WA
    School of Pathology and Laboratory Medicine, University of Western Australia)

  • Pimphen Charoen

    (Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine
    Faculty of Tropical Medicine, Mahidol University)

  • Petr Danecek

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Frank Dudbridge

    (Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine)

  • Vincenzo Forgetta

    (Lady Davis Institute, Jewish General Hospital, McGill University
    Biostatistics and Occupational Health, McGill University)

  • Celia Greenwood

    (Lady Davis Institute, Jewish General Hospital, McGill University
    Biostatistics and Occupational Health, McGill University
    McGill University)

  • Elin Grundberg

    (McGill University
    McGill University and Genome Quebec Innovation Centre)

  • Andrew D. Johnson

    (Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung and Blood Institute)

  • Jennie Hui

    (Pathwest Laboratory Medicine WA
    School of Pathology and Laboratory Medicine, University of Western Australia)

  • Ee M. Lim

    (Sir Charles Gairdner Hospital
    Pathwest Laboratory Medicine WA)

  • Shane McCarthy

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Dawn Muddyman

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Vijay Panicker

    (Sir Charles Gairdner Hospital)

  • John R.B. Perry

    (MRC Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital
    King's College London, ST Thomas' Campus)

  • Jordana T. Bell

    (King's College London, ST Thomas' Campus)

  • Wei Yuan

    (King's College London, ST Thomas' Campus)

  • Caroline Relton

    (MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove)

  • Tom Gaunt

    (MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove)

  • David Schlessinger

    (Laboratory of Genetics, NIA)

  • Goncalo Abecasis

    (Center for Statistical Genetics, University of Michigan)

  • Francesco Cucca

    (Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato
    Università di Sassari)

  • Gabriela L. Surdulescu

    (King's College London, ST Thomas' Campus)

  • Wolfram Woltersdorf

    (Facharzt für Laboratoriumsmedizin, Geschäftsführer amedes Ost, Halle/Leipzig GmbH)

  • Eleftheria Zeggini

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Hou-Feng Zheng

    (Biostatistics and Occupational Health, McGill University
    McGill University)

  • Daniela Toniolo

    (San Raffaele Research Institute
    Institute of Molecular Genetics-CNR)

  • Colin M. Dayan

    (Thyroid Research Group, Institute of Molecular & Experimental Medicine, Cardiff University School of Medicine, Cardiff University)

  • Silvia Naitza

    (Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato)

  • John P. Walsh

    (Sir Charles Gairdner Hospital
    School of Medicine and Pharmacology, University of Western Australia)

  • Tim Spector

    (King's College London, ST Thomas' Campus)

  • George Davey Smith

    (MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove)

  • Richard Durbin

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • J. Brent Richards

    (Lady Davis Institute, Jewish General Hospital, McGill University
    Biostatistics and Occupational Health, McGill University
    King's College London, ST Thomas' Campus
    McGill University)

  • Serena Sanna

    (Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato)

  • Nicole Soranzo

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Nicholas J. Timpson

    (MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove)

  • Scott G. Wilson

    (Sir Charles Gairdner Hospital
    School of Medicine and Pharmacology, University of Western Australia
    King's College London, ST Thomas' Campus)

Abstract

Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N=2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF≥1%) associated with TSH and FT4 (N=16,335). For TSH, we identify a novel variant in SYN2 (MAF=23.5%, P=6.15 × 10−9) and a new independent variant in PDE8B (MAF=10.4%, P=5.94 × 10−14). For FT4, we report a low-frequency variant near B4GALT6/SLC25A52 (MAF=3.2%, P=1.27 × 10−9) tagging a rare TTR variant (MAF=0.4%, P=2.14 × 10−11). All common variants explain ≥20% of the variance in TSH and FT4. Analysis of rare variants (MAF

Suggested Citation

  • Peter N. Taylor & Eleonora Porcu & Shelby Chew & Purdey J. Campbell & Michela Traglia & Suzanne J. Brown & Benjamin H. Mullin & Hashem A. Shihab & Josine Min & Klaudia Walter & Yasin Memari & Jie Huan, 2015. "Whole-genome sequence-based analysis of thyroid function," Nature Communications, Nature, vol. 6(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6681
    DOI: 10.1038/ncomms6681
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    Cited by:

    1. Rosalie B. T. M. Sterenborg & Inga Steinbrenner & Yong Li & Melissa N. Bujnis & Tatsuhiko Naito & Eirini Marouli & Tessel E. Galesloot & Oladapo Babajide & Laura Andreasen & Arne Astrup & Bjørn Olav Å, 2024. "Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Alexander T. Williams & Jing Chen & Kayesha Coley & Chiara Batini & Abril Izquierdo & Richard Packer & Erik Abner & Stavroula Kanoni & David J. Shepherd & Robert C. Free & Edward J. Hollox & Nigel J. , 2023. "Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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