Nat Commun.: co-auth.: group Reymond

 2018 Oct 26;9(1):4455. doi: 10.1038/s41467-018-06356-1.

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Teumer A1,2Chaker L3,4,5Groeneweg S3,5Li Y6Di Munno C3,7Barbieri C8Schultheiss UT6Traglia M8Ahluwalia TS9,10Akiyama M11Appel EVR10Arking DE12Arnold A13Astrup A14Beekman M15Beilby JP16,17Bekaert S18Boerwinkle E19Brown SJ20De Buyzere M21Campbell PJ20Ceresini G22Cerqueira C23Cucca F24,25Deary IJ26,27Deelen J15,28Eckardt KU29,30Ekici AB31Eriksson JG32,33,34Ferrrucci L35Fiers T36Fiorillo E24Ford I37Fox CS38,39Fuchsberger C40Galesloot TE41Gieger C42,43Gögele M40De Grandi A40Grarup N10Greiser KH44Haljas K45Hansen T10Harris SE26,46van Heemst D47den Heijer M48Hicks AA40den Hollander W49Homuth G50Hui J16,51Ikram MA4Ittermann T52,53Jensen RA54Jing J6,55Jukema JW56,57Kajantie E34,58,59Kamatani Y11,60Kasbohm E52,61Kaufman JM62Kiemeney LA41Kloppenburg M63,64Kronenberg F65Kubo M66Lahti J45Lapauw B62Li S67Liewald DCM26,27Lifelines Cohort StudyLim EM16,20Linneberg A23,68Marina M22Mascalzoni D40Matsuda K69Medenwald D70Meisinger C42,71Meulenbelt I49De Meyer T72Meyer Zu Schwabedissen HE73Mikolajczyk R70Moed M15Netea-Maier RT74Nolte IM75Okada Y11,76,77Pala M24Pattaro C40Pedersen O10Petersmann A78Porcu E24,79Postmus I80Pramstaller PP40Psaty BM81,82Ramos YFM49Rawal R42Redmond P27Richards JB83,84Rietzschel ER85,86Rivadeneira F4,5Roef G62Rotter JI87Sala CF8Schlessinger D88Selvin E89Slagboom PE15Soranzo N90Sørensen TIA10,91Spector TD84Starr JM26,92Stott DJ93Taes Y94Taliun D40Tanaka T35Thuesen B23Tiller D71Toniolo D8Uitterlinden AG4,5Visser WE3,5Walsh JP20,51Wilson SG20,51,84Wolffenbuttel BHR95Yang Q67Zheng HF96,97Cappola A98Peeters RP3,5Naitza S24Völzke H52,53Sanna S24,99Köttgen A6,100Visser TJ3,5Medici M3,4,5.

Abstract

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.

PMID: 30367059