Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.
Alexander TeumerLayal ChakerStefan GroenewegYong LiCelia Di MunnoCaterina BarbieriUlla T SchultheissMichela TragliaTarunveer Singh AhluwaliaMasato AkiyamaEmil Vincent R AppelDan E ArkingAlice ArnoldArnie AstrupMarian BeekmanJohn P BeilbySofie BekaertEric BoerwinkleSuzanne J BrownMarc De BuyzerePurdey J CampbellGraziano CeresiniCharlotte CerqueiraFrancesco CuccaIan J DearyJoris DeelenKai-Uwe EckardtArif Bülent EkiciJohan G ErikssonLuigi FerrrucciTom FiersEdoardo FiorilloIan FordCaroline S FoxChristian FuchsbergerTessel E GaleslootChristian GiegerMartin GögeleAlessandro De GrandiNiels GrarupKarin Halina GreiserKadri HaljasTorben HansenSarah E HarrisDiana van HeemstMartin den HeijerAndrew A HicksWouter den HollanderGeorg HomuthJennie HuiMohammad Arfan IkramTill IttermannRichard A JensenJiaojiao JingJohan Wouter JukemaEero KajantieYoichiro KamataniElisa KasbohmJean-Marc KaufmanLambertus A KiemeneyMargreet KloppenburgFlorian KronenbergMichiaki KuboJari M T LahtiBruno LapauwShuo LiDavid C M Liewaldnull nullEe Mun LimAllan LinnebergMichela MarinaDeborah MascalzoniKoichi MatsudaDaniel MedenwaldChrista MeisingerIngrid MeulenbeltTim De MeyerHenriette E Meyer Zu SchwabedissenRafael MikolajczykMatthijs MoedRomana T Netea-MaierIlja Maria NolteYukinori OkadaMauro PalaCristian PattaroOluf PedersenAstrid PetersmannEleonora PorcuIris PostmusPeter P PramstallerBruce M PsatyYolande Y F M RamosRajesh RawalPaul RedmondJohn Brent RichardsErnst R RietzschelFernando RivadeneiraGreet RoefJerome I RotterCinzia F SalaDavid SchlessingerElizabeth SelvinP Eline SlagboomNicole SoranzoThorkild I A SørensenTimothy D SpectorJohn M StarrDavid J StottYouri TaesDaniel TaliunToshiko TanakaBetina ThuesenDaniel TillerDaniela TonioloAndre G UitterlindenW Edward VisserJohn P WalshScott G WilsonBruce H R WolffenbuttelQiong YangHou-Feng ZhengAnne CappolaRobin P PeetersSilvia NaitzaHenry VölzkeSerena SannaAnna KottgenTheo J VisserMarco MediciPublished in: Nature communications (2018)
Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.