Association analysis identifies 65 new breast cancer risk loci

Kyriaki Michailidou, Sara Lindström, Joe Dennis, Jonathan Beesley, Shirley Hui, Siddhartha Kar, Audrey Lemaçon, Penny Soucy, Dylan Glubb, Asha Rostamianfar, Manjeet K. Bolla, Qin Wang, Jonathan Tyrer, Ed Dicks, Andrew Lee, Zhaoming Wang, Jamie Allen, Renske Keeman, Ursula Eilber, Juliet D. French & 233 others Xiao Qing Chen, Laura Fachal, Karen McCue, Amy E.Mc Cart Reed, Maya Ghoussaini, Jason S. Carroll, Xia Jiang, Hilary Finucane, Marcia Adams, Muriel A. Adank, Habibul Ahsan, Kristiina Aittomäki, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Kristan J. Aronson, Banu Arun, Paul L. Auer, François Bacot, Myrto Barrdahl, Caroline Baynes, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Leslie Bernstein, Carl Blomqvist, Natalia V. Bogdanova, Stig E. Bojesen, Bernardo Bonanni, Anne Lise Børresen-Dale, Judith S. Brand, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Louise Brinton, Per Broberg, Ian W. Brock, Annegien Broeks, Angela Brooks-Wilson, Sara Y. Brucker, Thomas Brüning, Barbara Burwinkel, Katja Butterbach, Qiuyin Cai, Hui Cai, Trinidad Caldés, Federico Canzian, Angel Carracedo, Brian D. Carter, Jose E. Castelao, Tsun L. Chan, Ting Yuan David Cheng, Kee Seng Chia, Ji Yeob Choi, Hans Christiansen, Christine L. Clarke, Margriet Collée, Don M. Conroy, Emilie Cordina-Duverger, Sten Cornelissen, David G. Cox, Angela Cox, Simon S. Cross, Julie M. Cunningham, Kamila Czene, Mary B. Daly, Peter Devilee, Kimberly F. Doheny, Thilo Dörk, Isabel Dos-Santos-Silva, Martine Dumont, Lorraine Durcan, Miriam Dwek, Diana M. Eccles, Arif B. Ekici, A. Heather Eliassen, Carolina Ellberg, Mingajeva Elvira, Christoph Engel, Mikael Eriksson, Peter A. Fasching, Jonine Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Henrik Flyger, Lin Fritschi, Valerie Gaborieau, Marike Gabrielson, Manuela Gago-Dominguez, Yu Tang Gao, Susan M. Gapstur, José A. García-Sáenz, Mia M. Gaudet, Vassilios Georgoulias, Graham G. Giles, Gord Glendon, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Grethe I.Grenaker Alnæs, Mervi Grip, Jacek Gronwald, Anne Grundy, Pascal Guénel, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Ute Hamann, Nathalie Hamel, Susan Hankinson, Patricia Harrington, Steven N. Hart, Jaana M. Hartikainen, Mikael Hartman, Alexander Hein, Jane Heyworth, Belynda Hicks, Peter Hillemanns, Dona N. Ho, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Ming Feng Hou, Chia Ni Hsiung, Guanmengqian Huang, Keith Humphreys, Junko Ishiguro, Hidemi Ito, Motoki Iwasaki, Hiroji Iwata, Anna Jakubowska, Wolfgang Janni, Esther M. John, Nichola Johnson, Kristine Jones, Michael Jones, Arja Jukkola-Vuorinen, Rudolf Kaaks, Maria Kabisch, Katarzyna Kaczmarek, Daehee Kang, Yoshio Kasuga, Michael J. Kerin, Sofia Khan, Elza Khusnutdinova, Johanna I. Kiiski, Sung Won Kim, Julia A. Knight, Veli Matti Kosma, Vessela N. Kristensen, Ute Krüger, Ava Kwong, Diether Lambrechts, Loic Le Marchand, Eunjung Lee, Min Hyuk Lee, Jong Won Lee, Chuen Neng Lee, Flavio Lejbkowicz, Jingmei Li, Jenna Lilyquist, Annika Lindblom, Jolanta Lissowska, Wing Yee Lo, Sibylle Loibl, Jirong Long, Artitaya Lophatananon, Jan Lubinski, Craig Luccarini, Michael P. Lux, Edmond S.K. Ma, Robert J. MacInnis, Tom Maishman, Enes Makalic, Kathleen E. Malone, Ivana Maleva Kostovska, Arto Mannermaa, Siranoush Manoukian, Jo Ann E. Manson, Sara Margolin, Shivaani Mariapun, Maria Elena Martinez, Keitaro Matsuo, Dimitrios Mavroudis, James McKay, Catriona McLean, Hanne Meijers-Heijboer, Alfons Meindl, Primitiva Menéndez, Usha Menon, Jeffery Meyer, Hui Miao, Nicola Miller, Nur Aishah Mohd Taib, Kenneth Muir, Anna Marie Mulligan, Claire Mulot, Susan L. Neuhausen, Heli Nevanlinna, Patrick Neven, Sune F. Nielsen, Dong Young Noh, Børge G. Nordestgaard, Aaron Norman, Olufunmilayo I. Olopade, Janet E. Olson, Håkan Olsson, Curtis Olswold, Nick Orr, V. Shane Pankratz, Sue K. Park, Tjoung Won Park-Simon, Rachel Lloyd, Jose I.A. Perez, Paolo Peterlongo, Julian Peto, Kelly Anne Phillips, Mila Pinchev, Dijana Plaseska-Karanfilska, Ross Prentice, Nadege Presneau, Darya Prokofyeva, Elizabeth Pugh, Katri Pylkäs, Brigitte Rack, Paolo Radice, Jennifer Stone, NBCS Collaborators, ABCTB Investigators, kConFab/AOCS Investigators

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

Original languageEnglish
Pages (from-to)92-94
Number of pages3
JournalNature
Volume551
Issue number7678
DOIs
Publication statusPublished - 2 Nov 2017

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Genes
Nucleotides
Polymorphism
Transcription factors
Binding sites
Tumors
Screening
Association reactions

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Michailidou, K., Lindström, S., Dennis, J., Beesley, J., Hui, S., Kar, S., ... kConFab/AOCS Investigators (2017). Association analysis identifies 65 new breast cancer risk loci. Nature, 551(7678), 92-94. https://doi.org/10.1038/nature24284
Michailidou, Kyriaki ; Lindström, Sara ; Dennis, Joe ; Beesley, Jonathan ; Hui, Shirley ; Kar, Siddhartha ; Lemaçon, Audrey ; Soucy, Penny ; Glubb, Dylan ; Rostamianfar, Asha ; Bolla, Manjeet K. ; Wang, Qin ; Tyrer, Jonathan ; Dicks, Ed ; Lee, Andrew ; Wang, Zhaoming ; Allen, Jamie ; Keeman, Renske ; Eilber, Ursula ; French, Juliet D. ; Chen, Xiao Qing ; Fachal, Laura ; McCue, Karen ; Reed, Amy E.Mc Cart ; Ghoussaini, Maya ; Carroll, Jason S. ; Jiang, Xia ; Finucane, Hilary ; Adams, Marcia ; Adank, Muriel A. ; Ahsan, Habibul ; Aittomäki, Kristiina ; Anton-Culver, Hoda ; Antonenkova, Natalia N. ; Arndt, Volker ; Aronson, Kristan J. ; Arun, Banu ; Auer, Paul L. ; Bacot, François ; Barrdahl, Myrto ; Baynes, Caroline ; Beckmann, Matthias W. ; Behrens, Sabine ; Benitez, Javier ; Bermisheva, Marina ; Bernstein, Leslie ; Blomqvist, Carl ; Bogdanova, Natalia V. ; Bojesen, Stig E. ; Bonanni, Bernardo ; Børresen-Dale, Anne Lise ; Brand, Judith S. ; Brauch, Hiltrud ; Brennan, Paul ; Brenner, Hermann ; Brinton, Louise ; Broberg, Per ; Brock, Ian W. ; Broeks, Annegien ; Brooks-Wilson, Angela ; Brucker, Sara Y. ; Brüning, Thomas ; Burwinkel, Barbara ; Butterbach, Katja ; Cai, Qiuyin ; Cai, Hui ; Caldés, Trinidad ; Canzian, Federico ; Carracedo, Angel ; Carter, Brian D. ; Castelao, Jose E. ; Chan, Tsun L. ; Cheng, Ting Yuan David ; Chia, Kee Seng ; Choi, Ji Yeob ; Christiansen, Hans ; Clarke, Christine L. ; Collée, Margriet ; Conroy, Don M. ; Cordina-Duverger, Emilie ; Cornelissen, Sten ; Cox, David G. ; Cox, Angela ; Cross, Simon S. ; Cunningham, Julie M. ; Czene, Kamila ; Daly, Mary B. ; Devilee, Peter ; Doheny, Kimberly F. ; Dörk, Thilo ; Dos-Santos-Silva, Isabel ; Dumont, Martine ; Durcan, Lorraine ; Dwek, Miriam ; Eccles, Diana M. ; Ekici, Arif B. ; Eliassen, A. Heather ; Ellberg, Carolina ; Elvira, Mingajeva ; Engel, Christoph ; Eriksson, Mikael ; Fasching, Peter A. ; Figueroa, Jonine ; Flesch-Janys, Dieter ; Fletcher, Olivia ; Flyger, Henrik ; Fritschi, Lin ; Gaborieau, Valerie ; Gabrielson, Marike ; Gago-Dominguez, Manuela ; Gao, Yu Tang ; Gapstur, Susan M. ; García-Sáenz, José A. ; Gaudet, Mia M. ; Georgoulias, Vassilios ; Giles, Graham G. ; Glendon, Gord ; Goldberg, Mark S. ; Goldgar, David E. ; González-Neira, Anna ; Alnæs, Grethe I.Grenaker ; Grip, Mervi ; Gronwald, Jacek ; Grundy, Anne ; Guénel, Pascal ; Haeberle, Lothar ; Hahnen, Eric ; Haiman, Christopher A. ; Håkansson, Niclas ; Hamann, Ute ; Hamel, Nathalie ; Hankinson, Susan ; Harrington, Patricia ; Hart, Steven N. ; Hartikainen, Jaana M. ; Hartman, Mikael ; Hein, Alexander ; Heyworth, Jane ; Hicks, Belynda ; Hillemanns, Peter ; Ho, Dona N. ; Hollestelle, Antoinette ; Hooning, Maartje J. ; Hoover, Robert N. ; Hopper, John L. ; Hou, Ming Feng ; Hsiung, Chia Ni ; Huang, Guanmengqian ; Humphreys, Keith ; Ishiguro, Junko ; Ito, Hidemi ; Iwasaki, Motoki ; Iwata, Hiroji ; Jakubowska, Anna ; Janni, Wolfgang ; John, Esther M. ; Johnson, Nichola ; Jones, Kristine ; Jones, Michael ; Jukkola-Vuorinen, Arja ; Kaaks, Rudolf ; Kabisch, Maria ; Kaczmarek, Katarzyna ; Kang, Daehee ; Kasuga, Yoshio ; Kerin, Michael J. ; Khan, Sofia ; Khusnutdinova, Elza ; Kiiski, Johanna I. ; Kim, Sung Won ; Knight, Julia A. ; Kosma, Veli Matti ; Kristensen, Vessela N. ; Krüger, Ute ; Kwong, Ava ; Lambrechts, Diether ; Le Marchand, Loic ; Lee, Eunjung ; Lee, Min Hyuk ; Lee, Jong Won ; Lee, Chuen Neng ; Lejbkowicz, Flavio ; Li, Jingmei ; Lilyquist, Jenna ; Lindblom, Annika ; Lissowska, Jolanta ; Lo, Wing Yee ; Loibl, Sibylle ; Long, Jirong ; Lophatananon, Artitaya ; Lubinski, Jan ; Luccarini, Craig ; Lux, Michael P. ; Ma, Edmond S.K. ; MacInnis, Robert J. ; Maishman, Tom ; Makalic, Enes ; Malone, Kathleen E. ; Kostovska, Ivana Maleva ; Mannermaa, Arto ; Manoukian, Siranoush ; Manson, Jo Ann E. ; Margolin, Sara ; Mariapun, Shivaani ; Martinez, Maria Elena ; Matsuo, Keitaro ; Mavroudis, Dimitrios ; McKay, James ; McLean, Catriona ; Meijers-Heijboer, Hanne ; Meindl, Alfons ; Menéndez, Primitiva ; Menon, Usha ; Meyer, Jeffery ; Miao, Hui ; Miller, Nicola ; Taib, Nur Aishah Mohd ; Muir, Kenneth ; Mulligan, Anna Marie ; Mulot, Claire ; Neuhausen, Susan L. ; Nevanlinna, Heli ; Neven, Patrick ; Nielsen, Sune F. ; Noh, Dong Young ; Nordestgaard, Børge G. ; Norman, Aaron ; Olopade, Olufunmilayo I. ; Olson, Janet E. ; Olsson, Håkan ; Olswold, Curtis ; Orr, Nick ; Pankratz, V. Shane ; Park, Sue K. ; Park-Simon, Tjoung Won ; Lloyd, Rachel ; Perez, Jose I.A. ; Peterlongo, Paolo ; Peto, Julian ; Phillips, Kelly Anne ; Pinchev, Mila ; Plaseska-Karanfilska, Dijana ; Prentice, Ross ; Presneau, Nadege ; Prokofyeva, Darya ; Pugh, Elizabeth ; Pylkäs, Katri ; Rack, Brigitte ; Radice, Paolo ; Stone, Jennifer ; NBCS Collaborators ; ABCTB Investigators ; kConFab/AOCS Investigators. / Association analysis identifies 65 new breast cancer risk loci. In: Nature. 2017 ; Vol. 551, No. 7678. pp. 92-94.
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title = "Association analysis identifies 65 new breast cancer risk loci",
abstract = "Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.",
author = "Kyriaki Michailidou and Sara Lindstr{\"o}m and Joe Dennis and Jonathan Beesley and Shirley Hui and Siddhartha Kar and Audrey Lema{\cc}on and Penny Soucy and Dylan Glubb and Asha Rostamianfar and Bolla, {Manjeet K.} and Qin Wang and Jonathan Tyrer and Ed Dicks and Andrew Lee and Zhaoming Wang and Jamie Allen and Renske Keeman and Ursula Eilber and French, {Juliet D.} and Chen, {Xiao Qing} and Laura Fachal and Karen McCue and Reed, {Amy E.Mc Cart} and Maya Ghoussaini and Carroll, {Jason S.} and Xia Jiang and Hilary Finucane and Marcia Adams and Adank, {Muriel A.} and Habibul Ahsan and Kristiina Aittom{\"a}ki and Hoda Anton-Culver and Antonenkova, {Natalia N.} and Volker Arndt and Aronson, {Kristan J.} and Banu Arun and Auer, {Paul L.} and Fran{\cc}ois Bacot and Myrto Barrdahl and Caroline Baynes and Beckmann, {Matthias W.} and Sabine Behrens and Javier Benitez and Marina Bermisheva and Leslie Bernstein and Carl Blomqvist and Bogdanova, {Natalia V.} and Bojesen, {Stig E.} and Bernardo Bonanni and B{\o}rresen-Dale, {Anne Lise} and Brand, {Judith S.} and Hiltrud Brauch and Paul Brennan and Hermann Brenner and Louise Brinton and Per Broberg and Brock, {Ian W.} and Annegien Broeks and Angela Brooks-Wilson and Brucker, {Sara Y.} and Thomas Br{\"u}ning and Barbara Burwinkel and Katja Butterbach and Qiuyin Cai and Hui Cai and Trinidad Cald{\'e}s and Federico Canzian and Angel Carracedo and Carter, {Brian D.} and Castelao, {Jose E.} and Chan, {Tsun L.} and Cheng, {Ting Yuan David} and Chia, {Kee Seng} and Choi, {Ji Yeob} and Hans Christiansen and Clarke, {Christine L.} and Margriet Coll{\'e}e and Conroy, {Don M.} and Emilie Cordina-Duverger and Sten Cornelissen and Cox, {David G.} and Angela Cox and Cross, {Simon S.} and Cunningham, {Julie M.} and Kamila Czene and Daly, {Mary B.} and Peter Devilee and Doheny, {Kimberly F.} and Thilo D{\"o}rk and Isabel Dos-Santos-Silva and Martine Dumont and Lorraine Durcan and Miriam Dwek and Eccles, {Diana M.} and Ekici, {Arif B.} and Eliassen, {A. Heather} and Carolina Ellberg and Mingajeva Elvira and Christoph Engel and Mikael Eriksson and Fasching, {Peter A.} and Jonine Figueroa and Dieter Flesch-Janys and Olivia Fletcher and Henrik Flyger and Lin Fritschi and Valerie Gaborieau and Marike Gabrielson and Manuela Gago-Dominguez and Gao, {Yu Tang} and Gapstur, {Susan M.} and Garc{\'i}a-S{\'a}enz, {Jos{\'e} A.} and Gaudet, {Mia M.} and Vassilios Georgoulias and Giles, {Graham G.} and Gord Glendon and Goldberg, {Mark S.} and Goldgar, {David E.} and Anna Gonz{\'a}lez-Neira and Aln{\ae}s, {Grethe I.Grenaker} and Mervi Grip and Jacek Gronwald and Anne Grundy and Pascal Gu{\'e}nel and Lothar Haeberle and Eric Hahnen and Haiman, {Christopher A.} and Niclas H{\aa}kansson and Ute Hamann and Nathalie Hamel and Susan Hankinson and Patricia Harrington and Hart, {Steven N.} and Hartikainen, {Jaana M.} and Mikael Hartman and Alexander Hein and Jane Heyworth and Belynda Hicks and Peter Hillemanns and Ho, {Dona N.} and Antoinette Hollestelle and Hooning, {Maartje J.} and Hoover, {Robert N.} and Hopper, {John L.} and Hou, {Ming Feng} and Hsiung, {Chia Ni} and Guanmengqian Huang and Keith Humphreys and Junko Ishiguro and Hidemi Ito and Motoki Iwasaki and Hiroji Iwata and Anna Jakubowska and Wolfgang Janni and John, {Esther M.} and Nichola Johnson and Kristine Jones and Michael Jones and Arja Jukkola-Vuorinen and Rudolf Kaaks and Maria Kabisch and Katarzyna Kaczmarek and Daehee Kang and Yoshio Kasuga and Kerin, {Michael J.} and Sofia Khan and Elza Khusnutdinova and Kiiski, {Johanna I.} and Kim, {Sung Won} and Knight, {Julia A.} and Kosma, {Veli Matti} and Kristensen, {Vessela N.} and Ute Kr{\"u}ger and Ava Kwong and Diether Lambrechts and {Le Marchand}, Loic and Eunjung Lee and Lee, {Min Hyuk} and Lee, {Jong Won} and Lee, {Chuen Neng} and Flavio Lejbkowicz and Jingmei Li and Jenna Lilyquist and Annika Lindblom and Jolanta Lissowska and Lo, {Wing Yee} and Sibylle Loibl and Jirong Long and Artitaya Lophatananon and Jan Lubinski and Craig Luccarini and Lux, {Michael P.} and Ma, {Edmond S.K.} and MacInnis, {Robert J.} and Tom Maishman and Enes Makalic and Malone, {Kathleen E.} and Kostovska, {Ivana Maleva} and Arto Mannermaa and Siranoush Manoukian and Manson, {Jo Ann E.} and Sara Margolin and Shivaani Mariapun and Martinez, {Maria Elena} and Keitaro Matsuo and Dimitrios Mavroudis and James McKay and Catriona McLean and Hanne Meijers-Heijboer and Alfons Meindl and Primitiva Men{\'e}ndez and Usha Menon and Jeffery Meyer and Hui Miao and Nicola Miller and Taib, {Nur Aishah Mohd} and Kenneth Muir and Mulligan, {Anna Marie} and Claire Mulot and Neuhausen, {Susan L.} and Heli Nevanlinna and Patrick Neven and Nielsen, {Sune F.} and Noh, {Dong Young} and Nordestgaard, {B{\o}rge G.} and Aaron Norman and Olopade, {Olufunmilayo I.} and Olson, {Janet E.} and H{\aa}kan Olsson and Curtis Olswold and Nick Orr and Pankratz, {V. Shane} and Park, {Sue K.} and Park-Simon, {Tjoung Won} and Rachel Lloyd and Perez, {Jose I.A.} and Paolo Peterlongo and Julian Peto and Phillips, {Kelly Anne} and Mila Pinchev and Dijana Plaseska-Karanfilska and Ross Prentice and Nadege Presneau and Darya Prokofyeva and Elizabeth Pugh and Katri Pylk{\"a}s and Brigitte Rack and Paolo Radice and Jennifer Stone and {NBCS Collaborators} and {ABCTB Investigators} and {kConFab/AOCS Investigators}",
year = "2017",
month = "11",
day = "2",
doi = "10.1038/nature24284",
language = "English",
volume = "551",
pages = "92--94",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group - Macmillan Publishers",
number = "7678",

}

Michailidou, K, Lindström, S, Dennis, J, Beesley, J, Hui, S, Kar, S, Lemaçon, A, Soucy, P, Glubb, D, Rostamianfar, A, Bolla, MK, Wang, Q, Tyrer, J, Dicks, E, Lee, A, Wang, Z, Allen, J, Keeman, R, Eilber, U, French, JD, Chen, XQ, Fachal, L, McCue, K, Reed, AEMC, Ghoussaini, M, Carroll, JS, Jiang, X, Finucane, H, Adams, M, Adank, MA, Ahsan, H, Aittomäki, K, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Arun, B, Auer, PL, Bacot, F, Barrdahl, M, Baynes, C, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bernstein, L, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bonanni, B, Børresen-Dale, AL, Brand, JS, Brauch, H, Brennan, P, Brenner, H, Brinton, L, Broberg, P, Brock, IW, Broeks, A, Brooks-Wilson, A, Brucker, SY, Brüning, T, Burwinkel, B, Butterbach, K, Cai, Q, Cai, H, Caldés, T, Canzian, F, Carracedo, A, Carter, BD, Castelao, JE, Chan, TL, Cheng, TYD, Chia, KS, Choi, JY, Christiansen, H, Clarke, CL, Collée, M, Conroy, DM, Cordina-Duverger, E, Cornelissen, S, Cox, DG, Cox, A, Cross, SS, Cunningham, JM, Czene, K, Daly, MB, Devilee, P, Doheny, KF, Dörk, T, Dos-Santos-Silva, I, Dumont, M, Durcan, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Ellberg, C, Elvira, M, Engel, C, Eriksson, M, Fasching, PA, Figueroa, J, Flesch-Janys, D, Fletcher, O, Flyger, H, Fritschi, L, Gaborieau, V, Gabrielson, M, Gago-Dominguez, M, Gao, YT, Gapstur, SM, García-Sáenz, JA, Gaudet, MM, Georgoulias, V, Giles, GG, Glendon, G, Goldberg, MS, Goldgar, DE, González-Neira, A, Alnæs, GIG, Grip, M, Gronwald, J, Grundy, A, Guénel, P, Haeberle, L, Hahnen, E, Haiman, CA, Håkansson, N, Hamann, U, Hamel, N, Hankinson, S, Harrington, P, Hart, SN, Hartikainen, JM, Hartman, M, Hein, A, Heyworth, J, Hicks, B, Hillemanns, P, Ho, DN, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Hou, MF, Hsiung, CN, Huang, G, Humphreys, K, Ishiguro, J, Ito, H, Iwasaki, M, Iwata, H, Jakubowska, A, Janni, W, John, EM, Johnson, N, Jones, K, Jones, M, Jukkola-Vuorinen, A, Kaaks, R, Kabisch, M, Kaczmarek, K, Kang, D, Kasuga, Y, Kerin, MJ, Khan, S, Khusnutdinova, E, Kiiski, JI, Kim, SW, Knight, JA, Kosma, VM, Kristensen, VN, Krüger, U, Kwong, A, Lambrechts, D, Le Marchand, L, Lee, E, Lee, MH, Lee, JW, Lee, CN, Lejbkowicz, F, Li, J, Lilyquist, J, Lindblom, A, Lissowska, J, Lo, WY, Loibl, S, Long, J, Lophatananon, A, Lubinski, J, Luccarini, C, Lux, MP, Ma, ESK, MacInnis, RJ, Maishman, T, Makalic, E, Malone, KE, Kostovska, IM, Mannermaa, A, Manoukian, S, Manson, JAE, Margolin, S, Mariapun, S, Martinez, ME, Matsuo, K, Mavroudis, D, McKay, J, McLean, C, Meijers-Heijboer, H, Meindl, A, Menéndez, P, Menon, U, Meyer, J, Miao, H, Miller, N, Taib, NAM, Muir, K, Mulligan, AM, Mulot, C, Neuhausen, SL, Nevanlinna, H, Neven, P, Nielsen, SF, Noh, DY, Nordestgaard, BG, Norman, A, Olopade, OI, Olson, JE, Olsson, H, Olswold, C, Orr, N, Pankratz, VS, Park, SK, Park-Simon, TW, Lloyd, R, Perez, JIA, Peterlongo, P, Peto, J, Phillips, KA, Pinchev, M, Plaseska-Karanfilska, D, Prentice, R, Presneau, N, Prokofyeva, D, Pugh, E, Pylkäs, K, Rack, B, Radice, P, Stone, J, NBCS Collaborators, ABCTB Investigators & kConFab/AOCS Investigators 2017, 'Association analysis identifies 65 new breast cancer risk loci' Nature, vol. 551, no. 7678, pp. 92-94. https://doi.org/10.1038/nature24284

Association analysis identifies 65 new breast cancer risk loci. / Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe; Beesley, Jonathan; Hui, Shirley; Kar, Siddhartha; Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K.; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D.; Chen, Xiao Qing; Fachal, Laura; McCue, Karen; Reed, Amy E.Mc Cart; Ghoussaini, Maya; Carroll, Jason S.; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Aronson, Kristan J.; Arun, Banu; Auer, Paul L.; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bonanni, Bernardo; Børresen-Dale, Anne Lise; Brand, Judith S.; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W.; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y.; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D.; Castelao, Jose E.; Chan, Tsun L.; Cheng, Ting Yuan David; Chia, Kee Seng; Choi, Ji Yeob; Christiansen, Hans; Clarke, Christine L.; Collée, Margriet; Conroy, Don M.; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G.; Cox, Angela; Cross, Simon S.; Cunningham, Julie M.; Czene, Kamila; Daly, Mary B.; Devilee, Peter; Doheny, Kimberly F.; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M.; Ekici, Arif B.; Eliassen, A. Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu Tang; Gapstur, Susan M.; García-Sáenz, José A.; Gaudet, Mia M.; Georgoulias, Vassilios; Giles, Graham G.; Glendon, Gord; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Alnæs, Grethe I.Grenaker; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A.; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N.; Hartikainen, Jaana M.; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Hou, Ming Feng; Hsiung, Chia Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M.; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J.; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I.; Kim, Sung Won; Knight, Julia A.; Kosma, Veli Matti; Kristensen, Vessela N.; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Le Marchand, Loic; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Lee, Chuen Neng; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P.; Ma, Edmond S.K.; MacInnis, Robert J.; Maishman, Tom; Makalic, Enes; Malone, Kathleen E.; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, Jo Ann E.; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Taib, Nur Aishah Mohd; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F.; Noh, Dong Young; Nordestgaard, Børge G.; Norman, Aaron; Olopade, Olufunmilayo I.; Olson, Janet E.; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V. Shane; Park, Sue K.; Park-Simon, Tjoung Won; Lloyd, Rachel; Perez, Jose I.A.; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofyeva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Stone, Jennifer; NBCS Collaborators; ABCTB Investigators; kConFab/AOCS Investigators.

In: Nature, Vol. 551, No. 7678, 02.11.2017, p. 92-94.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association analysis identifies 65 new breast cancer risk loci

AU - Michailidou, Kyriaki

AU - Lindström, Sara

AU - Dennis, Joe

AU - Beesley, Jonathan

AU - Hui, Shirley

AU - Kar, Siddhartha

AU - Lemaçon, Audrey

AU - Soucy, Penny

AU - Glubb, Dylan

AU - Rostamianfar, Asha

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Tyrer, Jonathan

AU - Dicks, Ed

AU - Lee, Andrew

AU - Wang, Zhaoming

AU - Allen, Jamie

AU - Keeman, Renske

AU - Eilber, Ursula

AU - French, Juliet D.

AU - Chen, Xiao Qing

AU - Fachal, Laura

AU - McCue, Karen

AU - Reed, Amy E.Mc Cart

AU - Ghoussaini, Maya

AU - Carroll, Jason S.

AU - Jiang, Xia

AU - Finucane, Hilary

AU - Adams, Marcia

AU - Adank, Muriel A.

AU - Ahsan, Habibul

AU - Aittomäki, Kristiina

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N.

AU - Arndt, Volker

AU - Aronson, Kristan J.

AU - Arun, Banu

AU - Auer, Paul L.

AU - Bacot, François

AU - Barrdahl, Myrto

AU - Baynes, Caroline

AU - Beckmann, Matthias W.

AU - Behrens, Sabine

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Bernstein, Leslie

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V.

AU - Bojesen, Stig E.

AU - Bonanni, Bernardo

AU - Børresen-Dale, Anne Lise

AU - Brand, Judith S.

AU - Brauch, Hiltrud

AU - Brennan, Paul

AU - Brenner, Hermann

AU - Brinton, Louise

AU - Broberg, Per

AU - Brock, Ian W.

AU - Broeks, Annegien

AU - Brooks-Wilson, Angela

AU - Brucker, Sara Y.

AU - Brüning, Thomas

AU - Burwinkel, Barbara

AU - Butterbach, Katja

AU - Cai, Qiuyin

AU - Cai, Hui

AU - Caldés, Trinidad

AU - Canzian, Federico

AU - Carracedo, Angel

AU - Carter, Brian D.

AU - Castelao, Jose E.

AU - Chan, Tsun L.

AU - Cheng, Ting Yuan David

AU - Chia, Kee Seng

AU - Choi, Ji Yeob

AU - Christiansen, Hans

AU - Clarke, Christine L.

AU - Collée, Margriet

AU - Conroy, Don M.

AU - Cordina-Duverger, Emilie

AU - Cornelissen, Sten

AU - Cox, David G.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Cunningham, Julie M.

AU - Czene, Kamila

AU - Daly, Mary B.

AU - Devilee, Peter

AU - Doheny, Kimberly F.

AU - Dörk, Thilo

AU - Dos-Santos-Silva, Isabel

AU - Dumont, Martine

AU - Durcan, Lorraine

AU - Dwek, Miriam

AU - Eccles, Diana M.

AU - Ekici, Arif B.

AU - Eliassen, A. Heather

AU - Ellberg, Carolina

AU - Elvira, Mingajeva

AU - Engel, Christoph

AU - Eriksson, Mikael

AU - Fasching, Peter A.

AU - Figueroa, Jonine

AU - Flesch-Janys, Dieter

AU - Fletcher, Olivia

AU - Flyger, Henrik

AU - Fritschi, Lin

AU - Gaborieau, Valerie

AU - Gabrielson, Marike

AU - Gago-Dominguez, Manuela

AU - Gao, Yu Tang

AU - Gapstur, Susan M.

AU - García-Sáenz, José A.

AU - Gaudet, Mia M.

AU - Georgoulias, Vassilios

AU - Giles, Graham G.

AU - Glendon, Gord

AU - Goldberg, Mark S.

AU - Goldgar, David E.

AU - González-Neira, Anna

AU - Alnæs, Grethe I.Grenaker

AU - Grip, Mervi

AU - Gronwald, Jacek

AU - Grundy, Anne

AU - Guénel, Pascal

AU - Haeberle, Lothar

AU - Hahnen, Eric

AU - Haiman, Christopher A.

AU - Håkansson, Niclas

AU - Hamann, Ute

AU - Hamel, Nathalie

AU - Hankinson, Susan

AU - Harrington, Patricia

AU - Hart, Steven N.

AU - Hartikainen, Jaana M.

AU - Hartman, Mikael

AU - Hein, Alexander

AU - Heyworth, Jane

AU - Hicks, Belynda

AU - Hillemanns, Peter

AU - Ho, Dona N.

AU - Hollestelle, Antoinette

AU - Hooning, Maartje J.

AU - Hoover, Robert N.

AU - Hopper, John L.

AU - Hou, Ming Feng

AU - Hsiung, Chia Ni

AU - Huang, Guanmengqian

AU - Humphreys, Keith

AU - Ishiguro, Junko

AU - Ito, Hidemi

AU - Iwasaki, Motoki

AU - Iwata, Hiroji

AU - Jakubowska, Anna

AU - Janni, Wolfgang

AU - John, Esther M.

AU - Johnson, Nichola

AU - Jones, Kristine

AU - Jones, Michael

AU - Jukkola-Vuorinen, Arja

AU - Kaaks, Rudolf

AU - Kabisch, Maria

AU - Kaczmarek, Katarzyna

AU - Kang, Daehee

AU - Kasuga, Yoshio

AU - Kerin, Michael J.

AU - Khan, Sofia

AU - Khusnutdinova, Elza

AU - Kiiski, Johanna I.

AU - Kim, Sung Won

AU - Knight, Julia A.

AU - Kosma, Veli Matti

AU - Kristensen, Vessela N.

AU - Krüger, Ute

AU - Kwong, Ava

AU - Lambrechts, Diether

AU - Le Marchand, Loic

AU - Lee, Eunjung

AU - Lee, Min Hyuk

AU - Lee, Jong Won

AU - Lee, Chuen Neng

AU - Lejbkowicz, Flavio

AU - Li, Jingmei

AU - Lilyquist, Jenna

AU - Lindblom, Annika

AU - Lissowska, Jolanta

AU - Lo, Wing Yee

AU - Loibl, Sibylle

AU - Long, Jirong

AU - Lophatananon, Artitaya

AU - Lubinski, Jan

AU - Luccarini, Craig

AU - Lux, Michael P.

AU - Ma, Edmond S.K.

AU - MacInnis, Robert J.

AU - Maishman, Tom

AU - Makalic, Enes

AU - Malone, Kathleen E.

AU - Kostovska, Ivana Maleva

AU - Mannermaa, Arto

AU - Manoukian, Siranoush

AU - Manson, Jo Ann E.

AU - Margolin, Sara

AU - Mariapun, Shivaani

AU - Martinez, Maria Elena

AU - Matsuo, Keitaro

AU - Mavroudis, Dimitrios

AU - McKay, James

AU - McLean, Catriona

AU - Meijers-Heijboer, Hanne

AU - Meindl, Alfons

AU - Menéndez, Primitiva

AU - Menon, Usha

AU - Meyer, Jeffery

AU - Miao, Hui

AU - Miller, Nicola

AU - Taib, Nur Aishah Mohd

AU - Muir, Kenneth

AU - Mulligan, Anna Marie

AU - Mulot, Claire

AU - Neuhausen, Susan L.

AU - Nevanlinna, Heli

AU - Neven, Patrick

AU - Nielsen, Sune F.

AU - Noh, Dong Young

AU - Nordestgaard, Børge G.

AU - Norman, Aaron

AU - Olopade, Olufunmilayo I.

AU - Olson, Janet E.

AU - Olsson, Håkan

AU - Olswold, Curtis

AU - Orr, Nick

AU - Pankratz, V. Shane

AU - Park, Sue K.

AU - Park-Simon, Tjoung Won

AU - Lloyd, Rachel

AU - Perez, Jose I.A.

AU - Peterlongo, Paolo

AU - Peto, Julian

AU - Phillips, Kelly Anne

AU - Pinchev, Mila

AU - Plaseska-Karanfilska, Dijana

AU - Prentice, Ross

AU - Presneau, Nadege

AU - Prokofyeva, Darya

AU - Pugh, Elizabeth

AU - Pylkäs, Katri

AU - Rack, Brigitte

AU - Radice, Paolo

AU - Stone, Jennifer

AU - NBCS Collaborators

AU - ABCTB Investigators

AU - kConFab/AOCS Investigators

PY - 2017/11/2

Y1 - 2017/11/2

N2 - Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

AB - Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

UR - http://www.scopus.com/inward/record.url?scp=85033379332&partnerID=8YFLogxK

U2 - 10.1038/nature24284

DO - 10.1038/nature24284

M3 - Article

VL - 551

SP - 92

EP - 94

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7678

ER -

Michailidou K, Lindström S, Dennis J, Beesley J, Hui S, Kar S et al. Association analysis identifies 65 new breast cancer risk loci. Nature. 2017 Nov 2;551(7678):92-94. https://doi.org/10.1038/nature24284