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

J. Gudmundsson; P. Sulem; V. Steinthorsdottir; J.T. Bergthorsson; G. Thorleifsson; A. Manolescu; T. Rafnar; D. Gudbjartsson; B.A. Agnarsson; A. Baker; A. Sigurdsson; K.R. Benediktsdottir; M. Jakobsdottir; T. Blondal; S.N. Stacey; A. Helgason; S. Gunnarsdottir; A. Olafsdottir; K.T. Kristinsson; B. Birgisdottir; S. Ghosh; S. Thorlacius; D. Magnusdottir; G. Stefansdottir; K. Kristjansson; Y. Bagger; R.L. Wilensky; M.P. Reilly; A.D. Morris; C.H. Kimber; A. Adeyemo; Y. Chen; J. Zhou; W.Y. So; P.C. Tong; M.C. Ng; T. Hansen; G. Andersen; K. Borch Johnsen; T. Jorgensen; A. Tres; F. Fuertes; M. Ruiz Echarri; L. Asin; B. Saez; E. van Boven; S. Klaver; D.W. Swinkels; K.K. Aben; T. Graif; J. Cashy; B.K. Suarez; O. van Vierssen Trip; M.L. Frigge; C. Ober; M.H. Hofker; C. Wijmenga; C. Christiansen; D.J. Rader; C.N. Palmer; C. Rotimi; J.C. Chan; O. Pedersen; G. Sigurdsson; R. Benediktsson; E. Jonsson; G.V. Einarsson; J.I. Mayordomo; W.J. Catalona; L.A. Kiemeney; R.B. Barkardottir; J.R. Gulcher; U. Thorsteinsdottir; A. Kong; K. Stefansson

doi:10.1038/ng2062

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

J. Gudmundsson^*, P. Sulem, V. Steinthorsdottir, J.T. Bergthorsson, G. Thorleifsson, A. Manolescu, T. Rafnar, D. Gudbjartsson, B.A. Agnarsson, A. Baker, A. Sigurdsson, K.R. Benediktsdottir, M. Jakobsdottir, T. Blondal, S.N. Stacey, A. Helgason, S. Gunnarsdottir, A. Olafsdottir, K.T. Kristinsson, B. BirgisdottirS. Ghosh, S. Thorlacius, D. Magnusdottir, G. Stefansdottir, K. Kristjansson, Y. Bagger, R.L. Wilensky, M.P. Reilly, A.D. Morris, C.H. Kimber, A. Adeyemo, Y. Chen, J. Zhou, W.Y. So, P.C. Tong, M.C. Ng, T. Hansen, G. Andersen, K. Borch Johnsen, T. Jorgensen, A. Tres, F. Fuertes, M. Ruiz Echarri, L. Asin, B. Saez, E. van Boven, S. Klaver, D.W. Swinkels, K.K. Aben, T. Graif, J. Cashy, B.K. Suarez, O. van Vierssen Trip, M.L. Frigge, C. Ober, M.H. Hofker, C. Wijmenga, C. Christiansen, D.J. Rader, C.N. Palmer, C. Rotimi, J.C. Chan, O. Pedersen, G. Sigurdsson, R. Benediktsson, E. Jonsson, G.V. Einarsson, J.I. Mayordomo, W.J. Catalona, L.A. Kiemeney, R.B. Barkardottir, J.R. Gulcher, U. Thorsteinsdottir, A. Kong, K. Stefansson

^*Corresponding author for this work

NUTRIM School of Nutrition and Translational Research in Metabolism

Research output: Contribution to journal › Article › Academic › peer-review

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 (HNF1beta), 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. AD - [1] deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. [2] These authors contributed equally to this work.

Original language	English
Pages (from-to)	977-983
Journal	Nature Genetics
Volume	39
Issue number	8
DOIs	https://doi.org/10.1038/ng2062
Publication status	Published - 1 Jan 2007

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10.1038/ng2062

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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

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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 (HNF1beta), 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. AD - [1] deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. [2] These authors contributed equally to this work.",

author = "J. Gudmundsson and P. Sulem and V. Steinthorsdottir and J.T. Bergthorsson and G. Thorleifsson and A. Manolescu and T. Rafnar and D. Gudbjartsson and B.A. Agnarsson and A. Baker and A. Sigurdsson and K.R. Benediktsdottir and M. Jakobsdottir and T. Blondal and S.N. Stacey and A. Helgason and S. Gunnarsdottir and A. Olafsdottir and K.T. Kristinsson and B. Birgisdottir and S. Ghosh and S. Thorlacius and D. Magnusdottir and G. Stefansdottir and K. Kristjansson and Y. Bagger and R.L. Wilensky and M.P. Reilly and A.D. Morris and C.H. Kimber and A. Adeyemo and Y. Chen and J. Zhou and W.Y. So and P.C. Tong and M.C. Ng and T. Hansen and G. Andersen and {Borch Johnsen}, K. and T. Jorgensen and A. Tres and F. Fuertes and {Ruiz Echarri}, M. and L. Asin and B. Saez and {van Boven}, E. and S. Klaver and D.W. Swinkels and K.K. Aben and T. Graif and J. Cashy and B.K. Suarez and {van Vierssen Trip}, O. and M.L. Frigge and C. Ober and M.H. Hofker and C. Wijmenga and C. Christiansen and D.J. Rader and C.N. Palmer and C. Rotimi and J.C. Chan and O. Pedersen and G. Sigurdsson and R. Benediktsson and E. Jonsson and G.V. Einarsson and J.I. Mayordomo and W.J. Catalona and L.A. Kiemeney and R.B. Barkardottir and J.R. Gulcher and U. Thorsteinsdottir and A. Kong and K. Stefansson",

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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, WY, Tong, PC, Ng, MC, Hansen, T, Andersen, G, Borch Johnsen, K, Jorgensen, T, Tres, A, Fuertes, F, Ruiz Echarri, M, Asin, L, Saez, B, van Boven, E, 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, CN, Rotimi, C, Chan, JC, 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, J.

AU - Sulem, P.

AU - Steinthorsdottir, V.

AU - Bergthorsson, J.T.

AU - Thorleifsson, G.

AU - Manolescu, A.

AU - Rafnar, T.

AU - Gudbjartsson, D.

AU - Agnarsson, B.A.

AU - Baker, A.

AU - Sigurdsson, A.

AU - Benediktsdottir, K.R.

AU - Jakobsdottir, M.

AU - Blondal, T.

AU - Stacey, S.N.

AU - Helgason, A.

AU - Gunnarsdottir, S.

AU - Olafsdottir, A.

AU - Kristinsson, K.T.

AU - Birgisdottir, B.

AU - Ghosh, S.

AU - Thorlacius, S.

AU - Magnusdottir, D.

AU - Stefansdottir, G.

AU - Kristjansson, K.

AU - Bagger, Y.

AU - Wilensky, R.L.

AU - Reilly, M.P.

AU - Morris, A.D.

AU - Kimber, C.H.

AU - Adeyemo, A.

AU - Chen, Y.

AU - Zhou, J.

AU - So, W.Y.

AU - Tong, P.C.

AU - Ng, M.C.

AU - Hansen, T.

AU - Andersen, G.

AU - Borch Johnsen, K.

AU - Jorgensen, T.

AU - Tres, A.

AU - Fuertes, F.

AU - Ruiz Echarri, M.

AU - Asin, L.

AU - Saez, B.

AU - van Boven, E.

AU - Klaver, S.

AU - Swinkels, D.W.

AU - Aben, K.K.

AU - Graif, T.

AU - Cashy, J.

AU - Suarez, B.K.

AU - van Vierssen Trip, O.

AU - Frigge, M.L.

AU - Ober, C.

AU - Hofker, M.H.

AU - Wijmenga, C.

AU - Christiansen, C.

AU - Rader, D.J.

AU - Palmer, C.N.

AU - Rotimi, C.

AU - Chan, J.C.

AU - Pedersen, O.

AU - Sigurdsson, G.

AU - Benediktsson, R.

AU - Jonsson, E.

AU - Einarsson, G.V.

AU - Mayordomo, J.I.

AU - Catalona, W.J.

AU - Kiemeney, L.A.

AU - Barkardottir, R.B.

AU - Gulcher, J.R.

AU - Thorsteinsdottir, U.

AU - Kong, A.

AU - Stefansson, K.

PY - 2007/1/1

Y1 - 2007/1/1

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 (HNF1beta), 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. AD - [1] deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. [2] These authors contributed equally to this work.

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 (HNF1beta), 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. AD - [1] deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. [2] These authors contributed equally to this work.

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 -