GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse genetic association with thyroid cancer
- Zhou, Wei
- Brumpton, Ben M
- Kabil, Omer
- Gudmundsson, Julius
- Thorleifsson, Gudmar
- Weinstock, Josh
- Zawistowski, Matthew
- Nielsen, Jonas B
- Chaker, Layal
- Medici, Marco
- Teumer, Alexander
- Naitza, Silvia
- Sanna, Serena
- Schultheiss, Ulla
- Cappola, Anne
- Karjalainen, Juha
- Kurki, Mitja I.
- Oneka, Morgan
- Taylor, Peter
- Fritsche, Lars G
- Graham, Sarah
- Wolford, Brooke
- Overton, William
- Rasheed, Humaira
- Haug, Eirin B
- Gabrielsen, Maiken
- Skogholt, Anne Heidi
- Surakka, Ida
- Davey Smith, George
- Pandit, Anita
- Roychowdhury, Tanmoy
- Hornsby, Whitney
- Jonasson, Jon G.
- Senter, Leigha
- Liyanarachchi, Sandya
- Ringel, Matthew
- Xu, LI
- Kiemeney, Lambertus A
- He, Huiling
- Netea-Maier, Romana
- Mayordomo, José I.
- Plantinga, Theo
- Hrafnkelsson, Jon
- Hjartarson, Hannes
- Sturgis, Erich
- Palotie, Aarno
- Daly, Mark
- Citterio, Cintia
- Arvan, Peter
- Brummett, Chad M
- Boehnke, Michael
- Chapelle, Albert de la
- Stefansson, Kari
- Hveem, Kristian
- Willer, Cristen J
- Asvold, Bjorn O
DOIAbstract
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 novel. 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 UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH in...
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