Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes

Julius Gudmundsson; Patrick Sulem; Valgerdur Steinthorsdottir; Jon T. Bergthorsson; Gudmar Thorleifsson; Andrei Manolescu; Thorunn Rafnar; Daniel Gudbjartsson; Bjarni A. Agnarsson; Adam Baker; Asgeir Sigurdsson; Kristrun R. Benediktsdottir; Margret Jakobsdottir; Thorarinn Blondal; Simon N. Stacey; Agnar Helgason; Steinunn Gunnarsdottir; Adalheidur Olafsdottir; Kari T. Kristinsson; Birgitta Birgisdottir; Shyamali Ghosh; Steinunn Thorlacius; Dana Magnusdottir; Gerdur Stefansdottir; Kristleifur Kristjansson; Yu Bagger; Robert L. Wilensky; Muredach P. Reilly; Andrew D. Morris; Charlotte H. Kimber; Adebowale Adeyemo; Yuanxiu Chen; Jie Zhou; Wing-Yee So; Peter C. Y. Tong; Maggie C. Y. Ng; Torben Hansen; Gitte Andersen; Knut Borch-Johnsen; Torben Jorgensen; Alejandro Tres; Fernando Fuertes; Manuel Ruiz-Echarri; Laura Asin; Berta Saez; Erica van Boven; Siem Klaver; Dorine W. Swinkels; Katja K. Aben; Theresa Graif; John Cashy; Brian K. Suarez; Onco van Vierssen Trip; Michael L. Frigge; Carole Ober; Marten H. Hofker; Cisca Wijmenga; Claus Christiansen; Daniel J. Rader; Colin N. A. Palmer; Charles Rotimi; Juliana C. N. Chan; Oluf Pedersen; Gunnar Sigurdsson; Rafn Benediktsson; Eirikur Jonsson; Gudmundur V. Einarsson; Jose I. Mayordomo; William J. Catalona; Lambertus A. Kiemeney; Rosa B. Barkardottir; Jeffrey R. Gulcher; Unnur Thorsteinsdottir; Augustine Kong; Kari Stefansson

doi:10.1038/ng2062

Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes

Julius Gudmundsson, Patrick Sulem, Valgerdur Steinthorsdottir, Jon T. Bergthorsson, Gudmar Thorleifsson, Andrei Manolescu, Thorunn Rafnar, Daniel Gudbjartsson, Bjarni A. Agnarsson, Adam Baker, Asgeir Sigurdsson, Kristrun R. Benediktsdottir, Margret Jakobsdottir, Thorarinn Blondal, Simon N. Stacey, Agnar Helgason, Steinunn Gunnarsdottir, Adalheidur Olafsdottir, Kari T. Kristinsson, Birgitta BirgisdottirShyamali Ghosh, Steinunn Thorlacius, Dana Magnusdottir, Gerdur Stefansdottir, Kristleifur Kristjansson, Yu Bagger, Robert L. Wilensky, Muredach P. Reilly, Andrew D. Morris, Charlotte H. Kimber, Adebowale Adeyemo, Yuanxiu Chen, Jie Zhou, Wing-Yee So, Peter C. Y. Tong, Maggie C. Y. Ng, Torben Hansen, Gitte Andersen, Knut Borch-Johnsen, Torben Jorgensen, Alejandro Tres, Fernando Fuertes, Manuel Ruiz-Echarri, Laura Asin, Berta Saez, Erica van Boven, Siem Klaver, Dorine W. Swinkels, Katja K. Aben, Theresa Graif, John Cashy, Brian K. Suarez, Onco van Vierssen Trip, Michael L. Frigge, Carole Ober, Marten H. Hofker, Cisca Wijmenga, Claus Christiansen, Daniel J. Rader, Colin N. A. Palmer, Charles Rotimi, Juliana C. N. Chan, Oluf Pedersen, Gunnar Sigurdsson, Rafn Benediktsson, Eirikur Jonsson, Gudmundur V. Einarsson, Jose I. Mayordomo, William J. Catalona, Lambertus A. Kiemeney, Rosa B. Barkardottir, Jeffrey R. Gulcher, Unnur Thorsteinsdottir, Augustine Kong, Kari Stefansson

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Abstract

We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1ß), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.

Original language	English
Pages (from-to)	977-983
Number of pages	7
Journal	Nature Genetics
Volume	39
Issue number	8
DOIs	https://doi.org/10.1038/ng2062
Publication status	Published - 2007

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Gudmundsson, J., Sulem, P., Steinthorsdottir, V., Bergthorsson, J. T., Thorleifsson, G., Manolescu, A., Rafnar, T., Gudbjartsson, D., Agnarsson, B. A., Baker, A., Sigurdsson, A., Benediktsdottir, K. R., Jakobsdottir, M., Blondal, T., Stacey, S. N., Helgason, A., Gunnarsdottir, S., Olafsdottir, A., Kristinsson, K. T., ... Stefansson, K. (2007). Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nature Genetics, 39(8), 977-983. https://doi.org/10.1038/ng2062

@article{7f4bbb4a19974091b619841319b84fe9,

title = "Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes",

abstract = "We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1{\ss}), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.",

author = "Julius Gudmundsson and Patrick Sulem and Valgerdur Steinthorsdottir and Bergthorsson, {Jon T.} and Gudmar Thorleifsson and Andrei Manolescu and Thorunn Rafnar and Daniel Gudbjartsson and Agnarsson, {Bjarni A.} and Adam Baker and Asgeir Sigurdsson and Benediktsdottir, {Kristrun R.} and Margret Jakobsdottir and Thorarinn Blondal and Stacey, {Simon N.} and Agnar Helgason and Steinunn Gunnarsdottir and Adalheidur Olafsdottir and Kristinsson, {Kari T.} and Birgitta Birgisdottir and Shyamali Ghosh and Steinunn Thorlacius and Dana Magnusdottir and Gerdur Stefansdottir and Kristleifur Kristjansson and Yu Bagger and Wilensky, {Robert L.} and Reilly, {Muredach P.} and Morris, {Andrew D.} and Kimber, {Charlotte H.} and Adebowale Adeyemo and Yuanxiu Chen and Jie Zhou and Wing-Yee So and Tong, {Peter C. Y.} and Ng, {Maggie C. Y.} and Torben Hansen and Gitte Andersen and Knut Borch-Johnsen and Torben Jorgensen and Alejandro Tres and Fernando Fuertes and Manuel Ruiz-Echarri and Laura Asin and Berta Saez and Boven, {Erica van} and Siem Klaver and Swinkels, {Dorine W.} and Aben, {Katja K.} and Theresa Graif and John Cashy and Suarez, {Brian K.} and {van Vierssen Trip}, Onco and Frigge, {Michael L.} and Carole Ober and Hofker, {Marten H.} and Cisca Wijmenga and Claus Christiansen and Rader, {Daniel J.} and Palmer, {Colin N. A.} and Charles Rotimi and Chan, {Juliana C. N.} and Oluf Pedersen and Gunnar Sigurdsson and Rafn Benediktsson and Eirikur Jonsson and Einarsson, {Gudmundur V.} and Mayordomo, {Jose I.} and Catalona, {William J.} and Kiemeney, {Lambertus A.} and Barkardottir, {Rosa B.} and Gulcher, {Jeffrey R.} and Unnur Thorsteinsdottir and Augustine Kong and Kari Stefansson",

note = "dc.publisher: Nature Publishing Group ",

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language = "English",

volume = "39",

pages = "977--983",

journal = "Nature Genetics",

issn = "1061-4036",

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Gudmundsson, J, Sulem, P, Steinthorsdottir, V, Bergthorsson, JT, Thorleifsson, G, Manolescu, A, Rafnar, T, Gudbjartsson, D, Agnarsson, BA, Baker, A, Sigurdsson, A, Benediktsdottir, KR, Jakobsdottir, M, Blondal, T, Stacey, SN, Helgason, A, Gunnarsdottir, S, Olafsdottir, A, Kristinsson, KT, Birgisdottir, B, Ghosh, S, Thorlacius, S, Magnusdottir, D, Stefansdottir, G, Kristjansson, K, Bagger, Y, Wilensky, RL, Reilly, MP, Morris, AD, Kimber, CH, Adeyemo, A, Chen, Y, Zhou, J, So, W-Y, Tong, PCY, Ng, MCY, Hansen, T, Andersen, G, Borch-Johnsen, K, Jorgensen, T, Tres, A, Fuertes, F, Ruiz-Echarri, M, Asin, L, Saez, B, Boven, EV, Klaver, S, Swinkels, DW, Aben, KK, Graif, T, Cashy, J, Suarez, BK, van Vierssen Trip, O, Frigge, ML, Ober, C, Hofker, MH, Wijmenga, C, Christiansen, C, Rader, DJ, Palmer, CNA, Rotimi, C, Chan, JCN, Pedersen, O, Sigurdsson, G, Benediktsson, R, Jonsson, E, Einarsson, GV, Mayordomo, JI, Catalona, WJ, Kiemeney, LA, Barkardottir, RB, Gulcher, JR, Thorsteinsdottir, U, Kong, A & Stefansson, K 2007, 'Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes', Nature Genetics, vol. 39, no. 8, pp. 977-983. https://doi.org/10.1038/ng2062

TY - JOUR

T1 - Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes

AU - Gudmundsson, Julius

AU - Sulem, Patrick

AU - Steinthorsdottir, Valgerdur

AU - Bergthorsson, Jon T.

AU - Thorleifsson, Gudmar

AU - Manolescu, Andrei

AU - Rafnar, Thorunn

AU - Gudbjartsson, Daniel

AU - Agnarsson, Bjarni A.

AU - Baker, Adam

AU - Sigurdsson, Asgeir

AU - Benediktsdottir, Kristrun R.

AU - Jakobsdottir, Margret

AU - Blondal, Thorarinn

AU - Stacey, Simon N.

AU - Helgason, Agnar

AU - Gunnarsdottir, Steinunn

AU - Olafsdottir, Adalheidur

AU - Kristinsson, Kari T.

AU - Birgisdottir, Birgitta

AU - Ghosh, Shyamali

AU - Thorlacius, Steinunn

AU - Magnusdottir, Dana

AU - Stefansdottir, Gerdur

AU - Kristjansson, Kristleifur

AU - Bagger, Yu

AU - Wilensky, Robert L.

AU - Reilly, Muredach P.

AU - Morris, Andrew D.

AU - Kimber, Charlotte H.

AU - Adeyemo, Adebowale

AU - Chen, Yuanxiu

AU - Zhou, Jie

AU - So, Wing-Yee

AU - Tong, Peter C. Y.

AU - Ng, Maggie C. Y.

AU - Hansen, Torben

AU - Andersen, Gitte

AU - Borch-Johnsen, Knut

AU - Jorgensen, Torben

AU - Tres, Alejandro

AU - Fuertes, Fernando

AU - Ruiz-Echarri, Manuel

AU - Asin, Laura

AU - Saez, Berta

AU - Boven, Erica van

AU - Klaver, Siem

AU - Swinkels, Dorine W.

AU - Aben, Katja K.

AU - Graif, Theresa

AU - Cashy, John

AU - Suarez, Brian K.

AU - van Vierssen Trip, Onco

AU - Frigge, Michael L.

AU - Ober, Carole

AU - Hofker, Marten H.

AU - Wijmenga, Cisca

AU - Christiansen, Claus

AU - Rader, Daniel J.

AU - Palmer, Colin N. A.

AU - Rotimi, Charles

AU - Chan, Juliana C. N.

AU - Pedersen, Oluf

AU - Sigurdsson, Gunnar

AU - Benediktsson, Rafn

AU - Jonsson, Eirikur

AU - Einarsson, Gudmundur V.

AU - Mayordomo, Jose I.

AU - Catalona, William J.

AU - Kiemeney, Lambertus A.

AU - Barkardottir, Rosa B.

AU - Gulcher, Jeffrey R.

AU - Thorsteinsdottir, Unnur

AU - Kong, Augustine

AU - Stefansson, Kari

N1 - dc.publisher: Nature Publishing Group

PY - 2007

Y1 - 2007

N2 - We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1ß), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.

AB - We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1ß), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.

U2 - 10.1038/ng2062

DO - 10.1038/ng2062

M3 - Article

SN - 1061-4036

VL - 39

SP - 977

EP - 983

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes

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