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

• Autores: 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 Eliana; Arvan, Peter; Brummett, Chad M.; Boehnke, Michael; de la Chapelle, Albert; Stefansson, Kari; Hveem, Kristian; Willer, Cristen J.; Åsvold, Bjørn Olav
• Año de publicación: 2020
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: THYROID; CANCER; TSH; THYROGLOBULIN
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Zhou, Wei. University of Michigan; Estados Unidos. University of Massachussets; Estados Unidos
Fil: Brumpton, Ben. University Of Bristol; Reino Unido. Norwegian University of Science and Technology; Noruega. Department of Thoracic Medicine, St. Olavs Hospital, Trondheim University Hospital; Noruega
Fil: Kabil, Omer. University of Michigan; Estados Unidos
Fil: Gudmundsson, Julius. deCODE genetics/AMGEN, 101, Reykjavik; Islandia
Fil: Thorleifsson, Gudmar. deCODE genetics/AMGEN, 101, Reykjavik; Islandia
Fil: Weinstock, Josh. University of Michigan; Estados Unidos
Fil: Zawistowski, Matthew. University of Michigan; Estados Unidos
Fil: Nielsen, Jonas B.. University of Michigan; Estados Unidos
Fil: Chaker, Layal. No especifíca;
Fil: Medici, Marco. No especifíca;
Fil: Teumer, Alexander. Institute for Community Medicine, University Medicine Greifswald, Greifswald; Alemania. DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald; Alemania
Fil: Naitza, Silvia. No especifíca;
Fil: Sanna, Serena. University of Groningen; Países Bajos
Fil: Schultheiss, Ulla T.. Albert Ludwigs University of Freiburg; Alemania
Fil: Cappola, Anne. University of Pennsylvania; Estados Unidos
Fil: Karjalainen, Juha. University of Helsinski; Finlandia. Massachusetts General Hospital ; Department Of Medicine ; Harvard Medical School; Estados Unidos
Fil: Kurki, Mitja. University of Helsinski; Finlandia. Massachusetts General Hospital ; Department Of Medicine ; Harvard Medical School; Estados Unidos
Fil: Oneka, Morgan. Michigan State University; Estados Unidos
Fil: Taylor, Peter. Cardiff University; Reino Unido
Fil: Fritsche, Lars G.. University of Michigan; Estados Unidos
Fil: Graham, Sarah E.. University of Michigan; Estados Unidos
Fil: Wolford, Brooke N.. University of Michigan; Estados Unidos
Fil: Overton, William. University of Michigan; Estados Unidos
Fil: Rasheed, Humaira. University Of Bristol; Reino Unido. Norwegian University of Science and Technology; Noruega
Fil: Haug, Eirin B.. University Of Bristol; Reino Unido. Norwegian University of Science and Technology; Noruega
Fil: Gabrielsen, Maiken E.. Norwegian University of Science and Technology; Noruega
Fil: Skogholt, Anne Heidi. Norwegian University of Science and Technology; Noruega
Fil: Surakka, Ida. University of Michigan; Estados Unidos
Fil: Davey Smith, George. University Of Bristol; Reino Unido
Fil: Pandit, Anita. University of Michigan; Estados Unidos
Fil: Roychowdhury, Tanmoy. University of Michigan; Estados Unidos
Fil: Hornsby, Whitney E.. University of Michigan; Estados Unidos
Fil: Jonasson, Jon G.. No especifíca;
Fil: Senter, Leigha. Ohio University; Estados Unidos
Fil: Liyanarachchi, Sandya. Ohio University; Estados Unidos
Fil: Ringel, Matthew D.. Ohio State University; Estados Unidos
Fil: Xu, Li. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados Unidos
Fil: Kiemeney, Lambertus A.. No especifíca;
Fil: He, Huiling. Ohio University; Estados Unidos
Fil: Netea-Maier, Romana T.. No especifíca;
Fil: Mayordomo, Jose I.. University of Colorado; Estados Unidos
Fil: Plantinga, Theo S.. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados Unidos
Fil: Hrafnkelsson, Jon. No especifíca;
Fil: Hjartarson, Hannes. No especifíca;
Fil: Sturgis, Erich M.. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados Unidos
Fil: Palotie, Aarno. Massachusetts General Hospital ; Department Of Medicine ; Harvard Medical School; Estados Unidos
Fil: Daly, Mark. Massachusetts General Hospital ; Department Of Medicine ; Harvard Medical School; Estados Unidos
Fil: Citterio, Cintia Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Arvan, Peter. University of Michigan; Estados Unidos
Fil: Brummett, Chad M.. University of Michigan; Estados Unidos
Fil: Boehnke, Michael. University of Michigan; Estados Unidos
Fil: de la Chapelle, Albert. Ohio University; Estados Unidos
Fil: Stefansson, Kari. No especifíca;
Fil: Hveem, Kristian. Norwegian University of Science and Technology; Noruega
Fil: Willer, Cristen J.. No especifíca;
Fil: Åsvold, Bjørn Olav. No especifíca;