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

Pedersen O; Lim EM; Visser WE; Brown SJ; Linneberg A; Volzke H; Mikolajczyk R; Pramstaller PP; Taliun D; Rivadeneira F; Pattaro C; Boerwinkle E; Kubo M; Kajantie E; Walsh JP; Haljas K; Kasbohm E; Rawal R; Kottgen A; Cucca F; Kiemeney LA; Jensen RA; Okadah Y; Eriksson JG; Homuth G; Postmus I; Wilson SG; Psaty BM; Starr JM; Arking DE; Ittermann T; Astrup A; zu Schwabedissen HEM; Ekici AB; Rotter JI; Fiorillo E; Peeters RP; Gieger C; den Heijer M; Wolffenbuttel BHR; Marina M; Medenwald D; Lapauw B; Appel EVR; Liewald DCM; Zheng HF; Yang Q; Medici M; Galesloot TE; Akiyama M; Campbell PJ; Sanna S; Sorensen TIA; De Meyer T; Ikrarm MA; Fiers T; Porcu E; Naitza S; Kloppenburg M; Stott DJ; Uitterlinden AG; Roef G; Kronenberg F; Grarup N; Ford I; Li S; Lahti J; Barbieri C; Schlessinger D; Richards JB; Sala CF; Fox CS; Rietzschel ER; Spector TD; Toniolo D; Cerqueira C; Taes Y; van Heemst D; Thuesen B; Tiller D; Kaufman JM; De Buyzere M; Deary IJ; Deelen J; den Hollander W; Pala M; Fuchsberger C; Ramos YFM; Di Munno C; Meisinger C; Hui JN; Nolte IM; Harris SE; Arnold A; Ahluwalia TS; Meulenbelt I; Jukema JW; Netea-Maier RT; De Grandi A; Soranzo N; Bekaert S; Moed M; Groeneweg S; Tanaka T; Mascalzoni D; Teumer A; Beekman M; Kamatani Y; Gogele M; Traglia M; Cappola A; Hicks AA; Jing J; Li Y; Petersmann A; Beilby JP; Chaker L; Greiser KH; Hansen T; Eckardt KU; Redmond P; Selvin E; Ceresini G; Ferrrucci L; Matsuda K; Visser TJ; Schultheiss UT; Slagboom PE
Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation

Pedersen O
Lim EM
Visser WE
Brown SJ
Linneberg A
Volzke H
Mikolajczyk R
Pramstaller PP
Taliun D
Rivadeneira F
Pattaro C
Boerwinkle E
Kubo M
Kajantie E
Walsh JP
Haljas K
Kasbohm E
Rawal R
Kottgen A
Cucca F
Kiemeney LA
Jensen RA
Okadah Y
Eriksson JG
Homuth G
Postmus I
Wilson SG
Psaty BM
Starr JM
Arking DE
Ittermann T
Astrup A
zu Schwabedissen HEM
Ekici AB
Rotter JI
Fiorillo E
Peeters RP
Gieger C
den Heijer M
Wolffenbuttel BHR
Marina M
Medenwald D
Lapauw B
Appel EVR
Liewald DCM
Zheng HF
Yang Q
Medici M
Galesloot TE
Akiyama M
Campbell PJ
Sanna S
Sorensen TIA
De Meyer T
Ikrarm MA
Fiers T
Porcu E
Naitza S
Kloppenburg M
Stott DJ
Uitterlinden AG
Roef G
Kronenberg F
Grarup N
Ford I
Li S
Lahti J
Barbieri C
Schlessinger D
Richards JB
Sala CF
Fox CS
Rietzschel ER
Spector TD
Toniolo D
Cerqueira C
Taes Y
van Heemst D
Thuesen B
Tiller D
Kaufman JM
De Buyzere M
Deary IJ
Deelen J
den Hollander W
Pala M
Fuchsberger C
Ramos YFM
Di Munno C
Meisinger C
Hui JN
Nolte IM
Harris SE
Arnold A
Ahluwalia TS
Meulenbelt I
Jukema JW
Netea-Maier RT
De Grandi A
Soranzo N
Bekaert S
Moed M
Groeneweg S
Tanaka T
Mascalzoni D
Teumer A
Beekman M
Kamatani Y
Gogele M
Traglia M
Cappola A
Hicks AA
Jing J
Li Y
Petersmann A
Beilby JP
Chaker L
Greiser KH
Hansen T
Eckardt KU
Redmond P
Selvin E
Ceresini G
Ferrrucci L
Matsuda K
Visser TJ
Schultheiss UT
Slagboom PE
Katso/Avaa
Lataukset: 

NATURE PUBLISHING GROUP
doi:10.1038/s41467-018-06356-1
URI
https://www.nature.com/articles/s41467-018-06356-1
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042822490
Tiivistelmä
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.
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