Evidence map›Paper›PMID 25743335›Full record

SynthesisNature communications2015

Whole-genome sequence-based analysis of thyroid function.

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 and 41 more

Erratum issuedOpen access · goldAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 60 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 7 pooled it
11.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 7 syntheses or guidelines pooled it, 105 citations in OpenAlex.

  1. Pooled it
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  6. Pooled it
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  8. Article
  9. Genetics of Thyroid Function: Relevance for Biology and Disease Management.The Journal of clinical endocrinology and metabolism · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Genetic determinants of thyroid function in children.European journal of endocrinology · 2023
    Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

51 authors at 20 institutions in 16 countries.

Peter N TaylorThyroid Research Group, Institute of Molecular &Experimental Medicine, Cardiff University School of Medicine, Cardiff University, Cardiff, UK.
Eleonora Porcu1] Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy [2] Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy [3] Center for Statistical Genetics, Biostatistics Department, University of Michigan, Ann Arbor, Michigan, USA.
Shelby ChewDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Purdey J CampbellDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Michela TragliaDivision of Genetics and Cell Biology, San Raffaele Research Institute, Milano, Italy.
Suzanne J BrownDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Benjamin H Mullin1] Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia [2] School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
Hashem A ShihabMRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK.
Josine MinMRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK.
Klaudia WalterWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Yasin MemariWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Jie HuangWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Michael R BarnesWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.ORCID 0000000190977381
John P Beilby1] Pathwest Laboratory Medicine WA, Nedlands, Western Australia, Australia [2] School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
Pimphen Charoen1] Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK [2] Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Petr DanecekWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Frank DudbridgeFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
Vincenzo Forgetta1] Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada [2] Department of Oncology, Department of Epidemiology, Biostatistics and Occupational Health, Jewish General Hospital, Lady Davis Institute, McGill University, Montréal, Québec, Canada.
Celia Greenwood1] Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada [2] Department of Oncology, Department of Epidemiology, Biostatistics and Occupational Health, Jewish General Hospital, Lady Davis Institute, McGill University, Montréal, Québec, Canada [3] Department of Human Genetics, McGill University, Montreal, Québec, Canada H3A1A5.
Elin Grundberg1] McGill University and Genome Quebec Innovation Centre, Montreal, Québec, Canada H3A1A5 [2] Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland, USA.
Andrew D JohnsonMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Box 285, Cambridge, UK.
Jennie Hui1] Pathwest Laboratory Medicine WA, Nedlands, Western Australia, Australia [2] School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
Ee M Lim1] Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia [2] Pathwest Laboratory Medicine WA, Nedlands, Western Australia, Australia.
Shane McCarthyWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Dawn MuddymanWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Vijay PanickerDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.ORCID 0000000315518411
John R B Perry1] Department of Twin Research and Genetic Epidemiology, King's College London, London, UK [2] Laboratory of Genetics, NIA, Baltimore, Maryland 21224, USA.
Jordana T BellLaboratory of Genetics, NIA, Baltimore, Maryland 21224, USA.
Wei YuanLaboratory of Genetics, NIA, Baltimore, Maryland 21224, USA.
Caroline ReltonMRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK.
Tom GauntMRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK.
David SchlessingerFacharzt für Laboratoriumsmedizin, Geschäftsführer amedes Ost, Halle/Leipzig GmbH, Leipziger Chaussee 191f, 06112 Halle (Saale), Germany.
Goncalo AbecasisCenter for Statistical Genetics, Biostatistics Department, University of Michigan, Ann Arbor, Michigan, USA.
Francesco Cucca1] Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy [2] Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy.
Gabriela L SurdulescuLaboratory of Genetics, NIA, Baltimore, Maryland 21224, USA.
Wolfram WoltersdorfInstitute of Molecular Genetics-CNR, Pavia, Italy.
Eleftheria ZegginiWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Hou-Feng Zheng1] Department of Oncology, Department of Epidemiology, Biostatistics and Occupational Health, Jewish General Hospital, Lady Davis Institute, McGill University, Montréal, Québec, Canada [2] Department of Pathology, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Daniela Toniolo1] Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano, Italy [2] Department of Psychiatry, Trinity Centre for Health Sciences, St James Hospital, James's Street, Dublin 8, Ireland.
Colin M DayanThyroid Research Group, Institute of Molecular &Experimental Medicine, Cardiff University School of Medicine, Cardiff University, Cardiff, UK.
Silvia NaitzaIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
John P Walsh1] Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia [2] School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
Tim SpectorLaboratory of Genetics, NIA, Baltimore, Maryland 21224, USA.
George Davey SmithMRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK.
Richard DurbinWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
J Brent Richards1] Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada [2] Department of Oncology, Department of Epidemiology, Biostatistics and Occupational Health, Jewish General Hospital, Lady Davis Institute, McGill University, Montréal, Québec, Canada [3] Laboratory of Genetics, NIA, Baltimore, Maryland 21224, USA [4] Department of Pathology, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Serena SannaIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
Nicole SoranzoWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.ORCID 0000000310953852
Nicholas J TimpsonMRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK.
Scott G Wilson1] Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia [2] School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia [3] Laboratory of Genetics, NIA, Baltimore, Maryland 21224, USA.
UK0K Consortium
Wellcome Sanger Institute · GBUniversity of Cambridge · GBKing's College London · GBUniversity College London · GBUniversity of Bristol · GBBGI Group (China) · CNCardiff University · GBCentre for Human Genetics · GBGreat Ormond Street Hospital · GBJewish General Hospital · CASir Charles Gairdner Hospital · AUThe University of Western Australia · AUEuropean Bioinformatics Institute · GBGuy's Hospital · GBQueen's University · CATranslational Research Institute · AUUniversity of Maryland, Baltimore · USInstitute of Genetic and Biomedical Research · ITRoyal Edinburgh Hospital · GBUniversity of Oxford · GB

Funding

Cardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3M
Aging-related Traits and Disease Risk Factors in a Sardinian Population CohortZIAAG000675 · NIA · NATIONAL INSTITUTE ON AGING · PI GOROSPE, MYRIAM · 2009 to 2021
$5.7M
British Heart Foundation RG/10/17/28553Medical Research Council MC_PC_15018Medical Research Council MC_U106179472Medical Research Council MC_UU_12012/5Medical Research Council MC_UU_12013/2Medical Research Council MC_UU_12013/3Medical Research Council MC_UU_12013/4Medical Research Council MC_UU_12013/8Medical Research Council MC_UU_12015/2Medical Research Council MR/K006215/1Medical Research Council MR/L010305/1Wellcome Trust 091551Wellcome Trust 095515Wellcome Trust 096599Wellcome Trust 098498Wellcome Trust 100140Wellcome Trust 100574Wellcome Trust 102215Wellcome Trust WT091310
6 · The paper itself

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<1%) using sequence kernel association testing reveals a novel association with FT4 in NRG1. Our results demonstrate that increased coverage in whole-genome sequence association studies identifies novel variants associated with thyroid function.

Indexed as

3',5'-Cyclic-AMP PhosphodiesterasesCohort StudiesDNA MethylationGenetic Association StudiesGenomicsHumansSynapsinsThyroid GlandThyrotropinThyroxineUnited Kingdom3',5'-Cyclic-AMP PhosphodiesterasesPDE8B protein, humanSYN2 protein, humanSynapsinsThyrotropinThyroxine

Identifiers

PMID25743335
PMCPMC4366514
OpenAlexW2109761709

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.