Nat Commun.: co-auth.: group Reymond

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 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 A1,2, Chaker L3,4,5, Groeneweg S3,5, Li Y6, Di Munno C3,7, Barbieri C8, Schultheiss UT6, Traglia M8, Ahluwalia TS9,10, Akiyama M11, Appel EVR10, Arking DE12, Arnold A13, Astrup A14, Beekman M15, Beilby JP16,17, Bekaert S18, Boerwinkle E19, Brown SJ20, De Buyzere M21, Campbell PJ20, Ceresini G22, Cerqueira C23, Cucca F24,25, Deary IJ26,27, Deelen J15,28, Eckardt KU29,30, Ekici AB31, Eriksson JG32,33,34, Ferrrucci L35, Fiers T36, Fiorillo E24, Ford I37, Fox CS38,39, Fuchsberger C40, Galesloot TE41, Gieger C42,43, Gögele M40, De Grandi A40, Grarup N10, Greiser KH44, Haljas K45, Hansen T10, Harris SE26,46, van Heemst D47, den Heijer M48, Hicks AA40, den Hollander W49, Homuth G50, Hui J16,51, Ikram MA4, Ittermann T52,53, Jensen RA54, Jing J6,55, Jukema JW56,57, Kajantie E34,58,59, Kamatani Y11,60, Kasbohm E52,61, Kaufman JM62, Kiemeney LA41, Kloppenburg M63,64, Kronenberg F65, Kubo M66, Lahti J45, Lapauw B62, Li S67, Liewald DCM26,27; Lifelines Cohort Study, Lim EM16,20, Linneberg A23,68, Marina M22, Mascalzoni D40, Matsuda K69, Medenwald D70, Meisinger C42,71, Meulenbelt I49, De Meyer T72, Meyer Zu Schwabedissen HE73, Mikolajczyk R70, Moed M15, Netea-Maier RT74, Nolte IM75, Okada Y11,76,77, Pala M24, Pattaro C40, Pedersen O10, Petersmann A78, Porcu E24,79, Postmus I80, Pramstaller PP40, Psaty BM81,82, Ramos YFM49, Rawal R42, Redmond P27, Richards JB83,84, Rietzschel ER85,86, Rivadeneira F4,5, Roef G62, Rotter JI87, Sala CF8, Schlessinger D88, Selvin E89, Slagboom PE15, Soranzo N90, Sørensen TIA10,91, Spector TD84, Starr JM26,92, Stott DJ93, Taes Y94, Taliun D40, Tanaka T35, Thuesen B23, Tiller D71, Toniolo D8, Uitterlinden AG4,5, Visser WE3,5, Walsh JP20,51, Wilson SG20,51,84, Wolffenbuttel BHR95, Yang Q67, Zheng HF96,97, Cappola A98, Peeters RP3,5, Naitza S24, Völzke H52,53, Sanna S24,99, Köttgen A6,100, Visser TJ3,5, Medici 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