Peter N. TaylorEleonora PorcuShelby ChewPurdey J. CampbellMichela TragliaSuzanne J. BrownBenjamin H. MullinHashem A. ShihabJosine MinKlaudia WalterYasin MemariJie HuangMichael R. BarnesJohn P. BeilbyPimphen CharoenPetr DanecekFrank DudbridgeVincenzo ForgettaCelia GreenwoodElin GrundbergAndrew D. JohnsonJennie HuiEe M. LimShane McCarthyDawn MuddymanVijay PanickerJohn R.B. PerryJordana T. BellWei YuanCaroline ReltonTom GauntDavid SchlessingerGoncalo AbecasisFrancesco CuccaGabriela L. SurdulescuWolfram WoltersdorfEleftheria ZegginiHou Feng ZhengDaniela TonioloColin M. DayanSilvia NaitzaJohn P. WalshTim SpectorGeorge Davey SmithRichard DurbinJ. Brent RichardsSerena SannaNicole SoranzoNicholas J. TimpsonScott G. WilsonSaeed Al TurkiCarl AndersonRichard AnneyDinu AntonyMaria Soler ArtigasMuhammad AyubSenduran BalasubramaniamJeffrey C. BarrettInês BarrosoPhil BealesJamie BenthamShoumo BhattacharyaEwan BirneyDouglas BlackwoodMartin BobrowElena BochukovaPatrick BoltonRebecca BoundsChris BoustredGerome BreenMattia CalissanoKeren CarssKrishna ChatterjeeLu ChenAntonio CiampiCardiff UniversityConsiglio Nazionale delle RicercheUniversita degli Studi di SassariUniversity of Michigan, Ann ArborSir Charles Gairdner HospitalIRCCS San Raffaele Scientific InstituteUniversity of Western AustraliaUniversity of BristolWellcome TrustBarts and The London School of Medicine and DentistryPathWest Laboratory Medicine WALondon School of Hygiene &amp; Tropical MedicineMahidol UniversityLady Davis Institute for Medical ResearchMcGill UniversityNational HeartAddenbrooke's HospitalKing's College LondonNIAIFB Halle GmbHKing Abdulaziz Medical City- RiyadhTrinity College DublinUCL Institute of Child HealthQueen's University, KingstonUniversity of CambridgeWellcome Trust Centre for Human GeneticsUniversity of EdinburghCambridge Institute for Medical ResearchUCLInstitut für HumangenetikEli Lilly and CompanyNHS Foundation TrustUniversity of SussexBiogen Inc.BGI-ShenzhenUniversity of QueenslandEdinburgh Medical School, Medical Research Council Human Genetics UnitQueen Mary, University of London2018-11-232018-11-232015-01-01Nature Communications. Vol.6, (2015)204117232-s2.0-84924347503https://repository.li.mahidol.ac.th/handle/20.500.14594/35655© 2015 Macmillan Publishers Limited. All rights reserved. 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryArticleSCOPUS10.1038/ncomms6681