Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Kyriaki Michailidou; Jonathan Beesley; Sara Lindstrom; Sander Canisius; Joe Dennis; Michael J. Lush; Mel J. Maranian; Manjeet K. Bolla; Qin Wang; Mitul Shah; Barbara J. Perkins; Kamila Czene; Mikael Eriksson; Hatef Darabi; Judith S. Brand; Stig E. Bojesen; Børge G. Nordestgaard; Henrik Flyger; Sune F. Nielsen; Nazneen Rahman; Clare Turnbull; Olivia Fletcher; Julian Peto; Lorna Gibson; Isabel Dos-Santos-Silva; Jenny Chang-Claude; Dieter Flesch-Janys; Anja Rudolph; Ursula Eilber; Sabine Behrens; Heli Nevanlinna; Taru A. Muranen; Kristiina Aittomäki; Carl Blomqvist; Sofia Khan; Kirsimari Aaltonen; Habibul Ahsan; Muhammad G. Kibriya; Alice S. Whittemore; Esther M. John; Kathleen E. Malone; Marilie D. Gammon; Regina M. Santella; Giske Ursin; Enes Makalic; Daniel F. Schmidt; Graham Casey; David J. Hunter; Susan M. Gapstur; Mia M. Gaudet; W. Ryan Diver; Christopher A. Haiman; Fredrick Schumacher; Brian E. Henderson; Loic Le Marchand; Christine D. Berg; Stephen J. Chanock; Jonine Figueroa; Robert N. Hoover; Diether Lambrechts; Patrick Neven; Hans Wildiers; Erik Van Limbergen; Marjanka K. Schmidt; Annegien Broeks; Senno Verhoef; Sten Cornelissen; Fergus J. Couch; Janet E. Olson; Emily Hallberg; Celine Vachon; Quinten Waisfisz; Hanne Meijers-Heijboer; Muriel A. Adank; Rob B. Van Der Luijt; Jingmei Li; Jianjun Liu; Keith Humphreys; Daehee Kang; Ji Yeob Choi; Sue K. Park; Keun Young Yoo; Keitaro Matsuo; Hidemi Ito; Hiroji Iwata; Kazuo Tajima; Pascal Guénel; Thérèse Truong; Claire Mulot; Marie Sanchez; Barbara Burwinkel; Frederik Marme; Harald Surowy; Christof Sohn; Anna H. Wu; Chiu Chen Tseng; David Van Den Berg; Daniel O. Stram; Anna González-Neira; Javier Benitez; M. Pilar Zamora; Jose Ignacio Arias Perez; Xiao Ou Shu; Wei Lu; Yu Tang Gao; Hui Cai; Angela Cox; Simon S. Cross; Malcolm W.R. Reed; Irene L. Andrulis; Julia A. Knight; Gord Glendon; Anna Marie Mulligan; Elinor J. Sawyer; Ian Tomlinson; Michael J. Kerin; Nicola Miller; Annika Lindblom; Sara Margolin; Soo Hwang Teo; Cheng Har Yip; Nur Aishah Mohd Taib; Gie Hooi Tan; Maartje J. Hooning; Antoinette Hollestelle; John W.M. Martens; J. Margriet Collée; William Blot; Lisa B. Signorello; Qiuyin Cai; John L. Hopper; Melissa C. Southey; Helen Tsimiklis; Carmel Apicella; Chen Yang Shen; Chia Ni Hsiung; Pei Ei Wu; Ming Feng Hou; Vessela N. Kristensen; Silje Nord; Grethe I.Grenaker Alnaes; Graham G. Giles; Roger L. Milne; Catriona McLean; Federico Canzian; Dimitrios Trichopoulos; Petra Peeters; Eiliv Lund; Malin Sund; Kay Tee Khaw; Marc J. Gunter; Domenico Palli; Lotte Maxild Mortensen; Laure Dossus; Jose Maria Huerta; Alfons Meindl; Rita K. Schmutzler; Christian Sutter; Rongxi Yang; Kenneth Muir; Artitaya Lophatananon; Sarah Stewart-Brown; Pornthep Siriwanarangsan; Mikael Hartman; Hui Miao; Kee Seng Chia; Ching Wan Chan; Peter A. Fasching; Alexander Hein; Matthias W. Beckmann; Lothar Haeberle; Hermann Brenner; Aida Karina Dieffenbach; Volker Arndt; Christa Stegmaier; Alan Ashworth; Nick Orr; Minouk J. Schoemaker; Anthony J. Swerdlow; Louise Brinton; Montserrat Garcia-Closas; Wei Zheng; Sandra L. Halverson; Martha Shrubsole; Jirong Long; Mark S. Goldberg; France Labrèche; Martine Dumont; Robert Winqvist; Katri Pylkäs; Arja Jukkola-Vuorinen; Mervi Grip; Hiltrud Brauch; Ute Hamann; Thomas Brüning; Paolo Radice; Paolo Peterlongo; Siranoush Manoukian; Loris Bernard; Natalia V. Bogdanova; Thilo Dörk; Arto Mannermaa; Vesa Kataja; Veli Matti Kosma; Jaana M. Hartikainen; Peter Devilee; Robert A.E.M. Tollenaar; Caroline Seynaeve; Christi J. Van Asperen; Anna Jakubowska; Jan Lubinski; Katarzyna Jaworska; Tomasz Huzarski; Suleeporn Sangrajrang; Valerie Gaborieau; Paul Brennan; James McKay; Susan Slager; Amanda E. Toland; Christine B. Ambrosone; Drakoulis Yannoukakos; Maria Kabisch; Diana Torres; Susan L. Neuhausen; Hoda Anton-Culver; Craig Luccarini; Caroline Baynes; Shahana Ahmed; Catherine S. Healey; Daniel C. Tessier; Daniel Vincent; Francois Bacot; Guillermo Pita; M. Rosario Alonso; Nuria Álvarez; Daniel Herrero; Jacques Simard; Paul P.D.P. Pharoah; Peter Kraft; Alison M. Dunning; Georgia Chenevix-Trench; Per Hall; Douglas F. Easton

doi:10.1038/ng.3242

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Kyriaki Michailidou, Jonathan Beesley, Sara Lindstrom, Sander Canisius, Joe Dennis, Michael J. Lush, Mel J. Maranian, Manjeet K. Bolla, Qin Wang, Mitul Shah, Barbara J. Perkins, Kamila Czene, Mikael Eriksson, Hatef Darabi, Judith S. Brand, Stig E. Bojesen, Børge G. Nordestgaard, Henrik Flyger, Sune F. Nielsen, Nazneen RahmanClare Turnbull, Olivia Fletcher, Julian Peto, Lorna Gibson, Isabel Dos-Santos-Silva, Jenny Chang-Claude, Dieter Flesch-Janys, Anja Rudolph, Ursula Eilber, Sabine Behrens, Heli Nevanlinna, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Sofia Khan, Kirsimari Aaltonen, Habibul Ahsan, Muhammad G. Kibriya, Alice S. Whittemore, Esther M. John, Kathleen E. Malone, Marilie D. Gammon, Regina M. Santella, Giske Ursin, Enes Makalic, Daniel F. Schmidt, Graham Casey, David J. Hunter, Susan M. Gapstur, Mia M. Gaudet, W. Ryan Diver, Christopher A. Haiman, Fredrick Schumacher, Brian E. Henderson, Loic Le Marchand, Christine D. Berg, Stephen J. Chanock, Jonine Figueroa, Robert N. Hoover, Diether Lambrechts, Patrick Neven, Hans Wildiers, Erik Van Limbergen, Marjanka K. Schmidt, Annegien Broeks, Senno Verhoef, Sten Cornelissen, Fergus J. Couch, Janet E. Olson, Emily Hallberg, Celine Vachon, Quinten Waisfisz, Hanne Meijers-Heijboer, Muriel A. Adank, Rob B. Van Der Luijt, Jingmei Li, Jianjun Liu, Keith Humphreys, Daehee Kang, Ji Yeob Choi, Sue K. Park, Keun Young Yoo, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Pascal Guénel, Thérèse Truong, Claire Mulot, Marie Sanchez, Barbara Burwinkel, Frederik Marme, Harald Surowy, Christof Sohn, Anna H. Wu, Chiu Chen Tseng, David Van Den Berg, Daniel O. Stram, Anna González-Neira, Javier Benitez, M. Pilar Zamora, Jose Ignacio Arias Perez, Xiao Ou Shu, Wei Lu, Yu Tang Gao, Hui Cai, Angela Cox, Simon S. Cross, Malcolm W.R. Reed, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Anna Marie Mulligan, Elinor J. Sawyer, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Annika Lindblom, Sara Margolin, Soo Hwang Teo, Cheng Har Yip, Nur Aishah Mohd Taib, Gie Hooi Tan, Maartje J. Hooning, Antoinette Hollestelle, John W.M. Martens, J. Margriet Collée, William Blot, Lisa B. Signorello, Qiuyin Cai, John L. Hopper, Melissa C. Southey, Helen Tsimiklis, Carmel Apicella, Chen Yang Shen, Chia Ni Hsiung, Pei Ei Wu, Ming Feng Hou, Vessela N. Kristensen, Silje Nord, Grethe I.Grenaker Alnaes, Graham G. Giles, Roger L. Milne, Catriona McLean, Federico Canzian, Dimitrios Trichopoulos, Petra Peeters, Eiliv Lund, Malin Sund, Kay Tee Khaw, Marc J. Gunter, Domenico Palli, Lotte Maxild Mortensen, Laure Dossus, Jose Maria Huerta, Alfons Meindl, Rita K. Schmutzler, Christian Sutter, Rongxi Yang, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Mikael Hartman, Hui Miao, Kee Seng Chia, Ching Wan Chan, Peter A. Fasching, Alexander Hein, Matthias W. Beckmann, Lothar Haeberle, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Alan Ashworth, Nick Orr, Minouk J. Schoemaker, Anthony J. Swerdlow, Louise Brinton, Montserrat Garcia-Closas, Wei Zheng, Sandra L. Halverson, Martha Shrubsole, Jirong Long, Mark S. Goldberg, France Labrèche, Martine Dumont, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Hiltrud Brauch, Ute Hamann, Thomas Brüning, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Loris Bernard, Natalia V. Bogdanova, Thilo Dörk, Arto Mannermaa, Vesa Kataja, Veli Matti Kosma, Jaana M. Hartikainen, Peter Devilee, Robert A.E.M. Tollenaar, Caroline Seynaeve, Christi J. Van Asperen, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska, Tomasz Huzarski, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Susan Slager, Amanda E. Toland, Christine B. Ambrosone, Drakoulis Yannoukakos, Maria Kabisch, Diana Torres, Susan L. Neuhausen, Hoda Anton-Culver, Craig Luccarini, Caroline Baynes, Shahana Ahmed, Catherine S. Healey, Daniel C. Tessier, Daniel Vincent, Francois Bacot, Guillermo Pita, M. Rosario Alonso, Nuria Álvarez, Daniel Herrero, Jacques Simard, Paul P.D.P. Pharoah, Peter Kraft, Alison M. Dunning, Georgia Chenevix-Trench, Per Hall, Douglas F. Easton^*

^*Corresponding author for this work

Research output: Contribution to journal › Letter › peer-review

452 Citations (Scopus)

Abstract

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10 â '8. Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

Original language	English
Pages (from-to)	373-380
Number of pages	8
Journal	Nature Genetics
Volume	47
Issue number	4
DOIs	https://doi.org/10.1038/ng.3242
Publication status	Published - 28 Apr 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.

ASJC Scopus subject areas

Genetics

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Michailidou, K., Beesley, J., Lindstrom, S., Canisius, S., Dennis, J., Lush, M. J., Maranian, M. J., Bolla, M. K., Wang, Q., Shah, M., Perkins, B. J., Czene, K., Eriksson, M., Darabi, H., Brand, J. S., Bojesen, S. E., Nordestgaard, B. G., Flyger, H., Nielsen, S. F., ... Easton, D. F. (2015). Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer. Nature Genetics, 47(4), 373-380. https://doi.org/10.1038/ng.3242

@article{5fbf23e0f1024887a90c3f7a2dd2c477,

title = "Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer",

abstract = "Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10 {\^a} '8. Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.",

author = "Kyriaki Michailidou and Jonathan Beesley and Sara Lindstrom and Sander Canisius and Joe Dennis and Lush, {Michael J.} and Maranian, {Mel J.} and Bolla, {Manjeet K.} and Qin Wang and Mitul Shah and Perkins, {Barbara J.} and Kamila Czene and Mikael Eriksson and Hatef Darabi and Brand, {Judith S.} and Bojesen, {Stig E.} and Nordestgaard, {B{\o}rge G.} and Henrik Flyger and Nielsen, {Sune F.} and Nazneen Rahman and Clare Turnbull and Olivia Fletcher and Julian Peto and Lorna Gibson and Isabel Dos-Santos-Silva and Jenny Chang-Claude and Dieter Flesch-Janys and Anja Rudolph and Ursula Eilber and Sabine Behrens and Heli Nevanlinna and Muranen, {Taru A.} and Kristiina Aittom{\"a}ki and Carl Blomqvist and Sofia Khan and Kirsimari Aaltonen and Habibul Ahsan and Kibriya, {Muhammad G.} and Whittemore, {Alice S.} and John, {Esther M.} and Malone, {Kathleen E.} and Gammon, {Marilie D.} and Santella, {Regina M.} and Giske Ursin and Enes Makalic and Schmidt, {Daniel F.} and Graham Casey and Hunter, {David J.} and Gapstur, {Susan M.} and Gaudet, {Mia M.} and Diver, {W. Ryan} and Haiman, {Christopher A.} and Fredrick Schumacher and Henderson, {Brian E.} and {Le Marchand}, Loic and Berg, {Christine D.} and Chanock, {Stephen J.} and Jonine Figueroa and Hoover, {Robert N.} and Diether Lambrechts and Patrick Neven and Hans Wildiers and {Van Limbergen}, Erik and Schmidt, {Marjanka K.} and Annegien Broeks and Senno Verhoef and Sten Cornelissen and Couch, {Fergus J.} and Olson, {Janet E.} and Emily Hallberg and Celine Vachon and Quinten Waisfisz and Hanne Meijers-Heijboer and Adank, {Muriel A.} and {Van Der Luijt}, {Rob B.} and Jingmei Li and Jianjun Liu and Keith Humphreys and Daehee Kang and Choi, {Ji Yeob} and Park, {Sue K.} and Yoo, {Keun Young} and Keitaro Matsuo and Hidemi Ito and Hiroji Iwata and Kazuo Tajima and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Claire Mulot and Marie Sanchez and Barbara Burwinkel and Frederik Marme and Harald Surowy and Christof Sohn and Wu, {Anna H.} and Tseng, {Chiu Chen} and {Van Den Berg}, David and Stram, {Daniel O.} and Anna Gonz{\'a}lez-Neira and Javier Benitez and {Pilar Zamora}, M. and Perez, {Jose Ignacio Arias} and Shu, {Xiao Ou} and Wei Lu and Gao, {Yu Tang} and Hui Cai and Angela Cox and Cross, {Simon S.} and Reed, {Malcolm W.R.} and Andrulis, {Irene L.} and Knight, {Julia A.} and Gord Glendon and Mulligan, {Anna Marie} and Sawyer, {Elinor J.} and Ian Tomlinson and Kerin, {Michael J.} and Nicola Miller and Annika Lindblom and Sara Margolin and Teo, {Soo Hwang} and Yip, {Cheng Har} and Taib, {Nur Aishah Mohd} and Tan, {Gie Hooi} and Hooning, {Maartje J.} and Antoinette Hollestelle and Martens, {John W.M.} and {Margriet Coll{\'e}e}, J. and William Blot and Signorello, {Lisa B.} and Qiuyin Cai and Hopper, {John L.} and Southey, {Melissa C.} and Helen Tsimiklis and Carmel Apicella and Shen, {Chen Yang} and Hsiung, {Chia Ni} and Wu, {Pei Ei} and Hou, {Ming Feng} and Kristensen, {Vessela N.} and Silje Nord and Alnaes, {Grethe I.Grenaker} and Giles, {Graham G.} and Milne, {Roger L.} and Catriona McLean and Federico Canzian and Dimitrios Trichopoulos and Petra Peeters and Eiliv Lund and Malin Sund and Khaw, {Kay Tee} and Gunter, {Marc J.} and Domenico Palli and Mortensen, {Lotte Maxild} and Laure Dossus and Huerta, {Jose Maria} and Alfons Meindl and Schmutzler, {Rita K.} and Christian Sutter and Rongxi Yang and Kenneth Muir and Artitaya Lophatananon and Sarah Stewart-Brown and Pornthep Siriwanarangsan and Mikael Hartman and Hui Miao and Chia, {Kee Seng} and Chan, {Ching Wan} and Fasching, {Peter A.} and Alexander Hein and Beckmann, {Matthias W.} and Lothar Haeberle and Hermann Brenner and Dieffenbach, {Aida Karina} and Volker Arndt and Christa Stegmaier and Alan Ashworth and Nick Orr and Schoemaker, {Minouk J.} and Swerdlow, {Anthony J.} and Louise Brinton and Montserrat Garcia-Closas and Wei Zheng and Halverson, {Sandra L.} and Martha Shrubsole and Jirong Long and Goldberg, {Mark S.} and France Labr{\`e}che and Martine Dumont and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Hiltrud Brauch and Ute Hamann and Thomas Br{\"u}ning and Paolo Radice and Paolo Peterlongo and Siranoush Manoukian and Loris Bernard and Bogdanova, {Natalia V.} and Thilo D{\"o}rk and Arto Mannermaa and Vesa Kataja and Kosma, {Veli Matti} and Hartikainen, {Jaana M.} and Peter Devilee and Tollenaar, {Robert A.E.M.} and Caroline Seynaeve and {Van Asperen}, {Christi J.} and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska and Tomasz Huzarski and Suleeporn Sangrajrang and Valerie Gaborieau and Paul Brennan and James McKay and Susan Slager and Toland, {Amanda E.} and Ambrosone, {Christine B.} and Drakoulis Yannoukakos and Maria Kabisch and Diana Torres and Neuhausen, {Susan L.} and Hoda Anton-Culver and Craig Luccarini and Caroline Baynes and Shahana Ahmed and Healey, {Catherine S.} and Tessier, {Daniel C.} and Daniel Vincent and Francois Bacot and Guillermo Pita and Alonso, {M. Rosario} and Nuria {\'A}lvarez and Daniel Herrero and Jacques Simard and Pharoah, {Paul P.D.P.} and Peter Kraft and Dunning, {Alison M.} and Georgia Chenevix-Trench and Per Hall and Easton, {Douglas F.}",

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doi = "10.1038/ng.3242",

language = "English",

volume = "47",

pages = "373--380",

journal = "Nature Genetics",

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publisher = "Nature Publishing Group",

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Michailidou, K, Beesley, J, Lindstrom, S, Canisius, S, Dennis, J, Lush, MJ, Maranian, MJ, Bolla, MK, Wang, Q, Shah, M, Perkins, BJ, Czene, K, Eriksson, M, Darabi, H, Brand, JS, Bojesen, SE, Nordestgaard, BG, Flyger, H, Nielsen, SF, Rahman, N, Turnbull, C, Fletcher, O, Peto, J, Gibson, L, Dos-Santos-Silva, I, Chang-Claude, J, Flesch-Janys, D, Rudolph, A, Eilber, U, Behrens, S, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Khan, S, Aaltonen, K, Ahsan, H, Kibriya, MG, Whittemore, AS, John, EM, Malone, KE, Gammon, MD, Santella, RM, Ursin, G, Makalic, E, Schmidt, DF, Casey, G, Hunter, DJ, Gapstur, SM, Gaudet, MM, Diver, WR, Haiman, CA, Schumacher, F, Henderson, BE, Le Marchand, L, Berg, CD, Chanock, SJ, Figueroa, J, Hoover, RN, Lambrechts, D, Neven, P, Wildiers, H, Van Limbergen, E, Schmidt, MK, Broeks, A, Verhoef, S, Cornelissen, S, Couch, FJ, Olson, JE, Hallberg, E, Vachon, C, Waisfisz, Q, Meijers-Heijboer, H, Adank, MA, Van Der Luijt, RB, Li, J, Liu, J, Humphreys, K, Kang, D, Choi, JY, Park, SK, Yoo, KY, Matsuo, K, Ito, H, Iwata, H, Tajima, K, Guénel, P, Truong, T, Mulot, C, Sanchez, M, Burwinkel, B, Marme, F, Surowy, H, Sohn, C, Wu, AH, Tseng, CC, Van Den Berg, D, Stram, DO, González-Neira, A, Benitez, J, Pilar Zamora, M, Perez, JIA, Shu, XO, Lu, W, Gao, YT, Cai, H, Cox, A, Cross, SS, Reed, MWR, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Lindblom, A, Margolin, S, Teo, SH, Yip, CH, Taib, NAM, Tan, GH, Hooning, MJ, Hollestelle, A, Martens, JWM, Margriet Collée, J, Blot, W, Signorello, LB, Cai, Q, Hopper, JL, Southey, MC, Tsimiklis, H, Apicella, C, Shen, CY, Hsiung, CN, Wu, PE, Hou, MF, Kristensen, VN, Nord, S, Alnaes, GIG, Giles, GG, Milne, RL, McLean, C, Canzian, F, Trichopoulos, D, Peeters, P, Lund, E, Sund, M, Khaw, KT, Gunter, MJ, Palli, D, Mortensen, LM, Dossus, L, Huerta, JM, Meindl, A, Schmutzler, RK, Sutter, C, Yang, R, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Hartman, M, Miao, H, Chia, KS, Chan, CW, Fasching, PA, Hein, A, Beckmann, MW, Haeberle, L, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Ashworth, A, Orr, N, Schoemaker, MJ, Swerdlow, AJ, Brinton, L, Garcia-Closas, M, Zheng, W, Halverson, SL, Shrubsole, M, Long, J, Goldberg, MS, Labrèche, F, Dumont, M, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Brauch, H, Hamann, U, Brüning, T, Radice, P, Peterlongo, P, Manoukian, S, Bernard, L, Bogdanova, NV, Dörk, T, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Van Asperen, CJ, Jakubowska, A, Lubinski, J, Jaworska, K, Huzarski, T, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Slager, S, Toland, AE, Ambrosone, CB, Yannoukakos, D, Kabisch, M, Torres, D, Neuhausen, SL, Anton-Culver, H, Luccarini, C, Baynes, C, Ahmed, S, Healey, CS, Tessier, DC, Vincent, D, Bacot, F, Pita, G, Alonso, MR, Álvarez, N, Herrero, D, Simard, J, Pharoah, PPDP, Kraft, P, Dunning, AM, Chenevix-Trench, G, Hall, P & Easton, DF 2015, 'Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer', Nature Genetics, vol. 47, no. 4, pp. 373-380. https://doi.org/10.1038/ng.3242

TY - JOUR

T1 - Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

AU - Michailidou, Kyriaki

AU - Beesley, Jonathan

AU - Lindstrom, Sara

AU - Canisius, Sander

AU - Dennis, Joe

AU - Lush, Michael J.

AU - Maranian, Mel J.

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Shah, Mitul

AU - Perkins, Barbara J.

AU - Czene, Kamila

AU - Eriksson, Mikael

AU - Darabi, Hatef

AU - Brand, Judith S.

AU - Bojesen, Stig E.

AU - Nordestgaard, Børge G.

AU - Flyger, Henrik

AU - Nielsen, Sune F.

AU - Rahman, Nazneen

AU - Turnbull, Clare

AU - Fletcher, Olivia

AU - Peto, Julian

AU - Gibson, Lorna

AU - Dos-Santos-Silva, Isabel

AU - Chang-Claude, Jenny

AU - Flesch-Janys, Dieter

AU - Rudolph, Anja

AU - Eilber, Ursula

AU - Behrens, Sabine

AU - Nevanlinna, Heli

AU - Muranen, Taru A.

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Khan, Sofia

AU - Aaltonen, Kirsimari

AU - Ahsan, Habibul

AU - Kibriya, Muhammad G.

AU - Whittemore, Alice S.

AU - John, Esther M.

AU - Malone, Kathleen E.

AU - Gammon, Marilie D.

AU - Santella, Regina M.

AU - Ursin, Giske

AU - Makalic, Enes

AU - Schmidt, Daniel F.

AU - Casey, Graham

AU - Hunter, David J.

AU - Gapstur, Susan M.

AU - Gaudet, Mia M.

AU - Diver, W. Ryan

AU - Haiman, Christopher A.

AU - Schumacher, Fredrick

AU - Henderson, Brian E.

AU - Le Marchand, Loic

AU - Berg, Christine D.

AU - Chanock, Stephen J.

AU - Figueroa, Jonine

AU - Hoover, Robert N.

AU - Lambrechts, Diether

AU - Neven, Patrick

AU - Wildiers, Hans

AU - Van Limbergen, Erik

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Verhoef, Senno

AU - Cornelissen, Sten

AU - Couch, Fergus J.

AU - Olson, Janet E.

AU - Hallberg, Emily

AU - Vachon, Celine

AU - Waisfisz, Quinten

AU - Meijers-Heijboer, Hanne

AU - Adank, Muriel A.

AU - Van Der Luijt, Rob B.

AU - Li, Jingmei

AU - Liu, Jianjun

AU - Humphreys, Keith

AU - Kang, Daehee

AU - Choi, Ji Yeob

AU - Park, Sue K.

AU - Yoo, Keun Young

AU - Matsuo, Keitaro

AU - Ito, Hidemi

AU - Iwata, Hiroji

AU - Tajima, Kazuo

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Mulot, Claire

AU - Sanchez, Marie

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Surowy, Harald

AU - Sohn, Christof

AU - Wu, Anna H.

AU - Tseng, Chiu Chen

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PY - 2015/4/28

Y1 - 2015/4/28

N2 - Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10 â '8. Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

AB - Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10 â '8. Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

U2 - 10.1038/ng.3242

DO - 10.1038/ng.3242

M3 - Letter

AN - SCOPUS:84930926883

SN - 1061-4036

VL - 47

SP - 373

EP - 380

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Abstract

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