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Discovery of common variants associated with low TSH levels and thyroid cancer risk.

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Authors
Gudmundsson, Julius
Sulem, Patrick
Gudbjartsson, Daniel F
Jonasson, Jon G
Masson, Gisli
He, Huiling
Jonasdottir, Aslaug
Sigurdsson, Asgeir
Stacey, Simon N
Johannsdottir, Hrefna
Helgadottir, Hafdis Th
Li, Wei
Nagy, Rebecca
Ringel, Matthew D
Kloos, Richard T
de Visser, Marieke C H
Plantinga, Theo S
den Heijer, Martin
Aguillo, Esperanza
Panadero, Angeles
Prats, Enrique
Garcia-Castaño, Almudena
De Juan, Ana
Rivera, Fernando
Walters, G Bragi
Bjarnason, Hjordis
Tryggvadottir, Laufey
Eyjolfsson, Gudmundur I
Bjornsdottir, Unnur S
Holm, Hilma
Olafsson, Isleifur
Kristjansson, Kristleifur
Kristvinsson, Hoskuldur
Magnusson, Olafur T
Thorleifsson, Gudmar
Gulcher, Jeffrey R
Kong, Augustine
Kiemeney, Lambertus A L M
Jonsson, Thorvaldur
Hjartarson, Hannes
Mayordomo, Jose I
Netea-Maier, Romana T
de la Chapelle, Albert
Hrafnkelsson, Jon
Thorsteinsdottir, Unnur
Rafnar, Thorunn
Stefansson, Kari
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Issue Date
2012-03

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Citation
Nat. Genet. 2012, 44(3):319-22
Abstract
To search for sequence variants conferring risk of nonmedullary thyroid cancer, we focused our analysis on 22 SNPs with a P < 5 × 10(-8) in a genome-wide association study on levels of thyroid stimulating hormone (TSH) in 27,758 Icelanders. Of those, rs965513 has previously been shown to associate with thyroid cancer. The remaining 21 SNPs were genotyped in 561 Icelandic individuals with thyroid cancer (cases) and up to 40,013 controls. Variants suggestively associated with thyroid cancer (P < 0.05) were genotyped in an additional 595 non-Icelandic cases and 2,604 controls. After combining the results, three variants were shown to associate with thyroid cancer: rs966423 on 2q35 (OR = 1.34; P(combined) = 1.3 × 10(-9)), rs2439302 on 8p12 (OR = 1.36; P(combined) = 2.0 × 10(-9)) and rs116909374 on 14q13.3 (OR = 2.09; P(combined) = 4.6 × 10(-11)), a region previously reported to contain an uncorrelated variant conferring risk of thyroid cancer. A strong association (P = 9.1 × 10(-91)) was observed between rs2439302 on 8p12 and expression of NRG1, which encodes the signaling protein neuregulin 1, in blood.
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Additional Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655412/
http://dx.doi.org/10.1038/ng.1046
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Archived with thanks to Nature genetics
ae974a485f413a2113503eed53cd6c53
10.1038/ng.1046
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