Pulse Brain · Growing Health Evidence Index
Tier 1 — Meta-analysis / systematic reviewPeer-reviewed

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Rosalie Sterenborg, Inga Steinbrenner, Yong Li, Melissa Bujnis, Tatsuhiko Naito, Eirini Marouli, Tessel E. Galesloot, Oladapo Babajide, Laura Andreasen, Arne Astrup, Bjørn Olav Åsvold, Stefania Bandinelli, Marian Beekman, John Beilby, Jette Bork‐Jensen, Thibaud Boutin, Jennifer A. Brody, Suzanne J. Brown, Ben Brumpton, Purdey J. Campbell, Anne Rentoumis Cappola, Graziano Ceresini, Layal Chaker, Daniel I. Chasman, Maria Pina Concas, Rodrigo Coutinho de Almeida, Simone Cross, Francesco Cucca, Ian J. Deary, Alisa D. Kjærgaard, Justin B. Echouffo‐Tcheugui, Christina Ellervik, Johan G. Eriksson, Luigi Ferrucci, Jan Freudenberg, GHS DiscovEHR, Christian Fuchsberger, Christian Gieger, Franco Giulianini, Martin Gögele, Sarah E. Graham, Niels Grarup, Ivana Gunjača, Torben Hansen, Barbara N Harding, Sarah E. Harris, Stig Haunsø, Caroline Hayward, Jennie Hui, Till Ittermann, J. Wouter Jukema, Eero Kajantie, Jørgen K. Kanters, Line Lund Kårhus, Lambertus A. Kiemeney, M. Kloppenburg, Brigitte Kühnel, Jari Lahti, Claudia Langenberg, Bruno Lapauw, Graham Leese, Shuo Li, David C. Liewald, Allan Linneberg, Jesus V. T. Lominchar, Jian’an Luan, Nicholas G. Martin, Antonela Matana, Marcel E. Meima, Thomas Meitinger, Ingrid Meulenbelt, Braxton D. Mitchell, Line T. Møllehave, Samia Mora, Silvia Naitza, Matthias Nauck, Romana T. Netea‐Maier, Raymond Noordam, Casia Nursyifa, Yukinori Okada, Stefano Onano, Areti Papadopoulou, Colin N. A. Palmer, Cristian Pattaro, Oluf Pedersen, Annette Peters, Maik Pietzner, Ozren Polašek, Peter P. Pramstaller, Bruce M. Psaty, Ante Punda, Debashree Ray, Paul Redmond, J. Brent Richards, Paul M. Ridker, Tom C. Russ, Kathleen A. Ryan, Morten S. Olesen, Ulla T. Schultheiß, Elizabeth Selvin

Nature Communications · 2024

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Summary

This genome-wide association meta-analysis of 271,040 European-ancestry individuals identified 259 novel genetic associations with TSH, 85 with FT4, and 62 with T3-related traits, substantially expanding knowledge of thyroid function genetics. Genetic correlation analyses distinguished between TSH-associated loci reflecting free T3-determined thyroid function and FT4 associations representing thyroid hormone metabolism. Mendelian randomization and polygenic risk score analyses revealed pleiotropic effects of genetically determined thyroid function variation on cardiovascular risk factors, autoimmune diseases, and cancer risk.

UK applicability

The study used European-ancestry populations and findings are directly applicable to the UK clinical and epidemiological context. Results may inform risk stratification and understanding of thyroid-related comorbidities in UK healthcare, though implementation would depend on validation in healthcare settings and consideration of ethnicity-specific effects.

Key measures

Genome-wide association signals for thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), T3/FT4 ratio; heritability explained (TSH 14.1%, FT4 6.0%, total T3 9.5%, free T3 1.1%); polygenic risk scores; Mendelian randomization estimates

Outcomes reported

The study identified 259 novel genetic associations with TSH, 85 with FT4, and 62 with T3-related traits through genome-wide association meta-analysis in 271,040 individuals. It examined causal relationships between genetically determined thyroid function variation and clinical outcomes including cardiovascular disease, autoimmune conditions, and cancer.

Theme
Nutrition & health
Subject
Micronutrients & dietary adequacy
Study type
Meta-analysis
Study design
Meta-analysis
Source type
Peer-reviewed study
Status
Published
Geography
Europe
System type
Human clinical
DOI
10.1038/s41467-024-44701-9
Catalogue ID
SNmoj1y5nt-7en71k

Topic tags

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