| Title: | Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease |
| Journal: | Nature Communications |
| Published: | 23 Oct 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37872160/ |
| DOI: | https://doi.org/10.1038/s41467-023-42284-5 |
| URL: | https://www.nature.com/articles/s41467-023-42284-5.pdf |
| Citations: | 5 (5 in last 2 years) as of 8 Aug 2024 |
Publication 9342
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Abstract
Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.</p>
32 Authors
- Alexander T. Williams
- Jing Chen
- Kayesha Coley
- Chiara Batini
- Abril Izquierdo
- Richard Packer
- Erik Abner
- Stavroula Kanoni
- David J. Shepherd
- Robert C. Free
- Edward J. Hollox
- Nigel J. Brunskill
- Ioanna Ntalla
- Nicola Reeve
- Christopher E. Brightling
- Laura Venn
- Emma Adams
- Catherine Bee
- Susan E. Wallace
- Manish Pareek
- Anna L. Hansell
- Tõnu Esko
- Daniel Stow
- Benjamin M. Jacobs
- David A. van Heel
- William Hennah
- Balasubramanya S. Rao
- Frank Dudbridge
- Louise V. Wain
- Nick Shrine
- Martin D. Tobin
- Catherine John
1 Application
| Application ID | Title |
|---|---|
| 43027 | Phenome-wide association studies to inform drug development |
Enabling scientific discoveries that improve human health