Details

Autor(en) / Beteiligte

• Zhou, Wei
• Brumpton, Ben
• 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 T
• Cappola, Anne
• Karjalainen, Juha
• Kurki, Mitja
• Oneka, Morgan
• Taylor, Peter
• Fritsche, Lars G
• Graham, Sarah E
• Wolford, Brooke N
• Overton, William
• Rasheed, Humaira
• Haug, Eirin B
• Gabrielsen, Maiken E
• Skogholt, Anne Heidi
• Surakka, Ida
• Davey Smith, George
• Pandit, Anita
• Roychowdhury, Tanmoy
• Hornsby, Whitney E
• Jonasson, Jon G
• Senter, Leigha
• Liyanarachchi, Sandya
• Ringel, Matthew D
• Xu, Li
• Kiemeney, Lambertus A
• He, Huiling
• Netea-Maier, Romana T
• Mayordomo, Jose I
• Plantinga, Theo S
• Hrafnkelsson, Jon
• Hjartarson, Hannes
• Sturgis, Erich M
• Palotie, Aarno
• Daly, Mark
• Citterio, Cintia E
• Arvan, Peter
• Brummett, Chad M
• Boehnke, Michael
• de la Chapelle, Albert
• Stefansson, Kari
• Hveem, Kristian
• Willer, Cristen J
• Åsvold, Bjørn Olav

Titel

GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer

Ist Teil von

• Nature communications, 2020-08, Vol.11 (1), p.3981-3981, Article 3981

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.