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Record W2896468934 · doi:10.1038/s41467-018-06356-1

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

2018· review· en· W2896468934 on OpenAlexaff
Alexander Teumer, Layal Chaker, Stefan Groeneweg, Yong Li, Celia Di Munno, Caterina Barbieri, Ulla T. Schultheiß, Michela Traglia, Tarunveer S. Ahluwalia, Masato Akiyama, Emil V. R. Appel, Dan E. Arking, Alice M. Arnold, Arne Astrup, Marian Beekman, John Beilby, Sofie Bekaert, Eric Boerwinkle, Suzanne J. Brown, Marc De Buyzere, Purdey J. Campbell, Graziano Ceresini, Charlotte Cerqueira, Francesco Cucca, Ian J. Deary, Joris Deelen, Kai‐Uwe Eckardt, Arif B. Ekici, Johan G. Eriksson, Luigi Ferrrucci, Tom Fiers, Edoardo Fiorillo, Ian Ford, Caroline S. Fox, Christian Fuchsberger, Tessel E. Galesloot, Christian Gieger, Martin Gögele, Alessandro De Grandi, Niels Grarup, Karin Halina Greiser, Kadri Haljas, Torben Hansen, Sarah E. Harris, Martin den Heijer, Andrew A. Hicks, Wouter den Hollander, Georg Homuth, Jennie Hui, M. Arfan Ikram, Till Ittermann, Richard A. Jensen, Jiaojiao Jing, J. Wouter Jukema, Eero Kajantie, Yoichiro Kamatani, Elisa Kasbohm, Jean‐Marc Kaufman, Lambertus A. Kiemeney, M. Kloppenburg, Florian Kronenberg, Michiaki Kubo, Jari Lahti, Bruno Lapauw, Shuo Li, David C. Liewald, Behrooz Z. Alizadeh, H. Marike Boezen, Lude Franke, Pim van der Harst, Gerjan Navis, Marianne G. Rots, Harold Snieder, Morris A. Swertz, Cisca Wijmenga, Ee Mun Lim, Allan Linneberg, Michela Marina, Deborah Mascalzoni, Koichi Matsuda, Daniel Medenwald, Christa Meisinger, Ingrid Meulenbelt, Tim De Meyer, Henriette E. Meyer zu Schwabedissen, Rafael Mikolajczyk, Matthijs Moed, Romana T. Netea‐Maier, Ilja M. Nolte, Yukinori Okada, Mauro Pala, Cristian Pattaro, Oluf Pedersen, Astrid Petersmann, Eleonora Porcu, Iris Postmus, Peter P. Pramstaller, Bruce M. Psaty, Y.F. Ramos, Rajesh Rawal, Paul Redmond, J. Brent Richards, Ernst Rietzschel, Fernando Rivadeneira, Greet Roef, Jerome I. Rotter, Cinzia Sala, David Schlessinger, Elizabeth Selvin, P. Eline Slagboom, Nicole Soranzo, Thorkild I. A. Sørensen, Timothy D. Spector, John M. Starr, David J. Stott, Youri Taes, Daniel Taliun, Toshiko Tanaka, Betina H. Thuesen, Daniel Tiller, Daniela Toniolo, André G. Uitterlinden, W. Edward Visser, John P. Walsh, Scott G. Wilson, Bruce H. R. Wolffenbuttel, Qiong Yang, Hou‐Feng Zheng, Anne Rentoumis Cappola, Robin P. Peeters, Silvia Naitza, Henry Völzke, Serena Sanna, Anna Köttgen, Theo J. Visser, Marco Medici

Bibliographic record

VenueNature Communications · 2018
Typereview
Languageen
FieldMedicine
TopicThyroid Disorders and Treatments
Canadian institutionsJewish General Hospital
FundersNational Heart, Lung, and Blood InstituteSteno Diabetes Center CopenhagenMedical Research CouncilNational Institute for Health and Care ResearchBiotechnology and Biological Sciences Research CouncilNovo Nordisk Fonden
KeywordsComputational biologyThyroidGenomeHormoneBioinformaticsBiologyMedicineGeneticsEndocrinologyGene

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.078
GPT teacher head0.430
Teacher spread0.352 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations289
Published2018
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicThyroid Disorders and TreatmentsFrench-language works237,207