| Title: | GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer |
| Journal: | Nature Communications |
| Published: | 7 Aug 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32769997/ |
| DOI: | https://doi.org/10.1038/s41467-020-17718-z |
| URL: | https://www.nature.com/articles/s41467-020-17718-z.pdf |
| Citations: | 103 (50 in last 2 years) as of 8 Aug 2024 |
Publication 5105
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Abstract
Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors.</p>
56 Authors
- Wei Zhou
- Ben Brumpton
- Omer Kabil
- Julius Gudmundsson
- Gudmar Thorleifsson
- Josh Weinstock
- Matthew Zawistowski
- Jonas B. Nielsen
- Layal Chaker
- Marco Medici
- Alexander Teumer
- Silvia Naitza
- Serena Sanna
- Ulla T. Schultheiss
- Anne Cappola
- Juha Karjalainen
- Mitja Kurki
- Morgan Oneka
- Peter Taylor
- Lars G. Fritsche
- Sarah E. Graham
- Brooke N. Wolford
- William Overton
- Humaira Rasheed
- Eirin B. Haug
- Maiken E. Gabrielsen
- Anne Heidi Skogholt
- Ida Surakka
- George Davey Smith
- Anita Pandit
- Tanmoy Roychowdhury
- Whitney E. Hornsby
- Jon G. Jonasson
- Leigha Senter
- Sandya Liyanarachchi
- Matthew D. Ringel
- Li Xu
- Lambertus A. Kiemeney
- Huiling He
- Romana T. Netea-Maier
- Jose I. Mayordomo
- Theo S. Plantinga
- Jon Hrafnkelsson
- Hannes Hjartarson
- Erich M. Sturgis
- Aarno Palotie
- Mark Daly
- Cintia E. Citterio
- Peter Arvan
- Chad M. Brummett
- Michael Boehnke
- Albert de la Chapelle
- Kari Stefansson
- Kristian Hveem
- Cristen J. Willer
- Bjørn Olav Åsvold
Enabling scientific discoveries that improve human health