A genome-wide association study yields five novel thyroid cancer risk loci

Julius Gudmundsson; Gudmar Thorleifsson; Jon K. Sigurdsson; Lilja Stefansdottir; Jon G. Jonasson; Sigurjon A. Gudjonsson; Daniel F. Gudbjartsson; Gisli Masson; Hrefna Johannsdottir; Gisli H. Halldorsson; Simon N. Stacey; Hannes Helgason; Patrick Sulem; Leigha Senter; Huiling He; Sandya Liyanarachchi; Matthew D. Ringel; Esperanza Aguillo; Angeles Panadero; Enrique Prats; Almudena Garcia-Castanõ; Ana De Juan; Fernando Rivera; Li Xu; Lambertus A. Kiemeney; Gudmundur I. Eyjolfsson; Olof Sigurdardottir; Isleifur Olafsson; Hoskuldur Kristvinsson; Romana T. Netea-Maier; Thorvaldur Jonsson; Jose I. Mayordomo; Theo S. Plantinga; Hannes Hjartarson; Jon Hrafnkelsson; Erich M. Sturgis; Unnur Thorsteinsdottir; Thorunn Rafnar; Albert De La Chapelle; Kari Stefansson

doi:10.1038/ncomms14517

A genome-wide association study yields five novel thyroid cancer risk loci

Julius Gudmundsson, Gudmar Thorleifsson, Jon K. Sigurdsson, Lilja Stefansdottir, Jon G. Jonasson, Sigurjon A. Gudjonsson, Daniel F. Gudbjartsson, Gisli Masson, Hrefna Johannsdottir, Gisli H. Halldorsson, Simon N. Stacey, Hannes Helgason, Patrick Sulem, Leigha Senter, Huiling He, Sandya Liyanarachchi, Matthew D. Ringel, Esperanza Aguillo, Angeles Panadero, Enrique PratsAlmudena Garcia-Castanõ, Ana De Juan, Fernando Rivera, Li Xu, Lambertus A. Kiemeney, Gudmundur I. Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Hoskuldur Kristvinsson, Romana T. Netea-Maier, Thorvaldur Jonsson, Jose I. Mayordomo, Theo S. Plantinga, Hannes Hjartarson, Jon Hrafnkelsson, Erich M. Sturgis, Unnur Thorsteinsdottir, Thorunn Rafnar, Albert De La Chapelle, Kari Stefansson

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Abstract

The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with P combined <3 × 10^-8): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 × 10^-7) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.

Original language	English (US)
Article number	14517
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14517
State	Published - Feb 14 2017

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Gudmundsson, J., Thorleifsson, G., Sigurdsson, J. K., Stefansdottir, L., Jonasson, J. G., Gudjonsson, S. A., Gudbjartsson, D. F., Masson, G., Johannsdottir, H., Halldorsson, G. H., Stacey, S. N., Helgason, H., Sulem, P., Senter, L., He, H., Liyanarachchi, S., Ringel, M. D., Aguillo, E., Panadero, A., ... Stefansson, K. (2017). A genome-wide association study yields five novel thyroid cancer risk loci. Nature communications, 8, Article 14517. https://doi.org/10.1038/ncomms14517

Gudmundsson, J, Thorleifsson, G, Sigurdsson, JK, Stefansdottir, L, Jonasson, JG, Gudjonsson, SA, Gudbjartsson, DF, Masson, G, Johannsdottir, H, Halldorsson, GH, Stacey, SN, Helgason, H, Sulem, P, Senter, L, He, H, Liyanarachchi, S, Ringel, MD, Aguillo, E, Panadero, A, Prats, E, Garcia-Castanõ, A, De Juan, A, Rivera, F, Xu, L, Kiemeney, LA, Eyjolfsson, GI, Sigurdardottir, O, Olafsson, I, Kristvinsson, H, Netea-Maier, RT, Jonsson, T, Mayordomo, JI, Plantinga, TS, Hjartarson, H, Hrafnkelsson, J, Sturgis, EM, Thorsteinsdottir, U, Rafnar, T, De La Chapelle, A & Stefansson, K 2017, 'A genome-wide association study yields five novel thyroid cancer risk loci', Nature communications, vol. 8, 14517. https://doi.org/10.1038/ncomms14517

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title = "A genome-wide association study yields five novel thyroid cancer risk loci",

abstract = "The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with P combined <3 × 10-8): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 × 10-7) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.",

author = "Julius Gudmundsson and Gudmar Thorleifsson and Sigurdsson, {Jon K.} and Lilja Stefansdottir and Jonasson, {Jon G.} and Gudjonsson, {Sigurjon A.} and Gudbjartsson, {Daniel F.} and Gisli Masson and Hrefna Johannsdottir and Halldorsson, {Gisli H.} and Stacey, {Simon N.} and Hannes Helgason and Patrick Sulem and Leigha Senter and Huiling He and Sandya Liyanarachchi and Ringel, {Matthew D.} and Esperanza Aguillo and Angeles Panadero and Enrique Prats and Almudena Garcia-Castan{\~o} and {De Juan}, Ana and Fernando Rivera and Li Xu and Kiemeney, {Lambertus A.} and Eyjolfsson, {Gudmundur I.} and Olof Sigurdardottir and Isleifur Olafsson and Hoskuldur Kristvinsson and Netea-Maier, {Romana T.} and Thorvaldur Jonsson and Mayordomo, {Jose I.} and Plantinga, {Theo S.} and Hannes Hjartarson and Jon Hrafnkelsson and Sturgis, {Erich M.} and Unnur Thorsteinsdottir and Thorunn Rafnar and {De La Chapelle}, Albert and Kari Stefansson",

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doi = "10.1038/ncomms14517",

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T1 - A genome-wide association study yields five novel thyroid cancer risk loci

AU - Gudmundsson, Julius

AU - Thorleifsson, Gudmar

AU - Sigurdsson, Jon K.

AU - Stefansdottir, Lilja

AU - Jonasson, Jon G.

AU - Gudjonsson, Sigurjon A.

AU - Gudbjartsson, Daniel F.

AU - Masson, Gisli

AU - Johannsdottir, Hrefna

AU - Halldorsson, Gisli H.

AU - Stacey, Simon N.

AU - Helgason, Hannes

AU - Sulem, Patrick

AU - Senter, Leigha

AU - He, Huiling

AU - Liyanarachchi, Sandya

AU - Ringel, Matthew D.

AU - Aguillo, Esperanza

AU - Panadero, Angeles

AU - Prats, Enrique

AU - Garcia-Castanõ, Almudena

AU - De Juan, Ana

AU - Rivera, Fernando

AU - Xu, Li

AU - Kiemeney, Lambertus A.

AU - Eyjolfsson, Gudmundur I.

AU - Sigurdardottir, Olof

AU - Olafsson, Isleifur

AU - Kristvinsson, Hoskuldur

AU - Netea-Maier, Romana T.

AU - Jonsson, Thorvaldur

AU - Mayordomo, Jose I.

AU - Plantinga, Theo S.

AU - Hjartarson, Hannes

AU - Hrafnkelsson, Jon

AU - Sturgis, Erich M.

AU - Thorsteinsdottir, Unnur

AU - Rafnar, Thorunn

AU - De La Chapelle, Albert

AU - Stefansson, Kari

PY - 2017/2/14

Y1 - 2017/2/14

N2 - The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with P combined <3 × 10-8): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 × 10-7) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.

AB - The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with P combined <3 × 10-8): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 × 10-7) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.

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A genome-wide association study yields five novel thyroid cancer risk loci

Abstract

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MD Anderson CCSG core facilities

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