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

被引：198

作者：

Gudmundsson, Julius ^{[1
]}

Sulem, Patrick ^{[1
]}

Gudbjartsson, Daniel F. ^{[1
]}

Jonasson, Jon G. ^{[2
,3
,4
]}

Masson, Gisli ^{[1
]}

He, Huiling ^{[5
]}

Jonasdottir, Aslaug ^{[1
]}

Sigurdsson, Asgeir ^{[1
]}

Stacey, Simon N. ^{[1
]}

Johannsdottir, Hrefna ^{[1
]}

Helgadottir, Hafdis Th ^{[1
]}

Li, Wei ^{[5
]}

Nagy, Rebecca ^{[5
]}

Ringel, Matthew D. ^{[6
]}

Kloos, Richard T. ^{[6
]}

de Visser, Marieke C. H. ^{[7
]}

Plantinga, Theo S. ^{[8
]}

den Heijer, Martin ^{[7
,15
]}

Aguillo, Esperanza ^{[9
]}

Panadero, Angeles ^{[10
]}

Prats, Enrique ^{[11
]}

Garcia-Castano, Almudena ^{[12
]}

De Juan, Ana ^{[12
]}

Rivera, Fernando ^{[12
]}

Walters, G. Bragi ^{[1
]}

Bjarnason, Hjordis ^{[1
]}

Tryggvadottir, Laufey ^{[3
,4
]}

Eyjolfsson, Gudmundur I. ^{[13
]}

Bjornsdottir, Unnur S. ^{[3
]}

Holm, Hilma ^{[1
]}

Olafsson, Isleifur ^{[2
]}

Kristjansson, Kristleifur ^{[1
]}

Kristvinsson, Hoskuldur ^{[2
]}

Magnusson, Olafur T. ^{[1
]}

Thorleifsson, Gudmar ^{[1
]}

Gulcher, Jeffrey R. ^{[1
]}

Kong, Augustine ^{[1
]}

Kiemeney, Lambertus A. L. M. ^{[7
]}

Jonsson, Thorvaldur ^{[2
,3
]}

Hjartarson, Hannes ^{[2
]}

Mayordomo, Jose I. ^{[14
]}

Netea-Maier, Romana T. ^{[15
]}

de la Chapelle, Albert ^{[5
]}

Hrafnkelsson, Jon ^{[2
]}

Thorsteinsdottir, Unnur ^{[1
,3
]}

Rafnar, Thorunn ^{[1
]}

Stefansson, Kari ^{[1
,3
]}

机构：

[1] deCODE Genet, Reykjavik, Iceland

[2] Lanspitali Univ Hosp, Reykjavik, Iceland

[3] Univ Iceland, Fac Med, Reykjavik, Iceland

[4] Iceland Canc Registry, Reykjavik, Iceland

[5] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA

[6] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA

[7] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, NL-6525 ED Nijmegen, Netherlands

[8] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands

[9] Univ Hosp, Div Endocrinol, Zaragoza, Spain

[10] Ciudad Coria Hosp, Div Med Oncol, Coria, Spain

[11] Univ Hosp, Div Nucl Med, Zaragoza, Spain

[12] Marques de Valdecilla Univ Hosp, Div Med Oncol, Santander, Spain

[13] Lab Mjodd, Reykjavik, Iceland

[14] Univ Zaragoza, Div Med Oncol, Zaragoza, Spain

[15] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands

来源：

NATURE GENETICS | 2012年 / 44卷 / 03期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS; GENE-EXPRESSION; SERUM TSH; CARCINOMA; INDIVIDUALS; POPULATIONS; ICELAND; DISEASE;

D O I：

10.1038/ng.1046

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To search for sequence variants conferring risk of nonmedullary thyroid cancer, we focused our analysis on 22 SNPs with a P < 5 x 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 x 10(-9)), rs2439302 on 8p12 (OR = 1.36; P-combined = 2.0 x 10(-9)) and rs116909374 on 14q13.3 (OR = 2.09; P-combined = 4.6 x 10(-11)), a region previously reported to contain an uncorrelated variant conferring risk of thyroid cancer. A strong association (P = 9.1 x 10(-91)) was observed between rs2439302 on 8p12 and expression of NRG1, which encodes the signaling protein neuregulin 1, in blood.

引用

页码：319 / U126

页数：6

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