Association analysis identifies 65 new breast cancer risk loci
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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; Qing Chen, Xiao; Fachal, Laura; McCue, Karen; McCart Reed, Amy E; 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; David Cheng, Ting-Yuan; Seng Chia, Kee; 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; Grenaker Alnæs, Grethe I; 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; Neng Lee, Chuen; 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, JoAnn 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; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J T; Saloustros, Emmanouil; Sandler, Dale P; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Daniel F; Schmutzler, Rita K; Schneeweiss, Andreas; Schoemaker, Minouk J; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E; Shrubsole, Martha J; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C; Spinelli, John J; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A; Tengström, Maria; Teo, Soo H; Beth Terry, Mary; Tessier, Daniel C; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A E M; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J; Van Den Berg, David; van den Ouweland, Ans M W; van der Kolk, Lizet; van der Luijt, Rob B; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R; Wendt, Camilla; Whittemore, Alice S; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R; Har Yip, Cheng; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R; Antoniou, Antonis C; Droit, Arnaud; Andrulis, Irene L; Amos, Christopher I; Couch, Fergus J; Pharoah, Paul D P; Chang-Claude, Jenny; Hall, Per; Hunter, David J; Milne, Roger L; García-Closas, Montserrat; Schmidt, Marjanka K; Chanock, Stephen J; Dunning, Alison M; Edwards, Stacey L; Bader, Gary D; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F; NBCS Collaborators.
in: NATURE, Jahrgang 551, Nr. 7678, 02.11.2017, S. 92-94.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 - Qing Chen, Xiao
AU - Fachal, Laura
AU - McCue, Karen
AU - McCart Reed, Amy E
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 - David Cheng, Ting-Yuan
AU - Seng Chia, Kee
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 - Grenaker Alnæs, Grethe I
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 - Neng Lee, Chuen
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, JoAnn 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 - Rahman, Nazneen
AU - Rennert, Gadi
AU - Rennert, Hedy S
AU - Rhenius, Valerie
AU - Romero, Atocha
AU - Romm, Jane
AU - Ruddy, Kathryn J
AU - Rüdiger, Thomas
AU - Rudolph, Anja
AU - Ruebner, Matthias
AU - Rutgers, Emiel J T
AU - Saloustros, Emmanouil
AU - Sandler, Dale P
AU - Sangrajrang, Suleeporn
AU - Sawyer, Elinor J
AU - Schmidt, Daniel F
AU - Schmutzler, Rita K
AU - Schneeweiss, Andreas
AU - Schoemaker, Minouk J
AU - Schumacher, Fredrick
AU - Schürmann, Peter
AU - Scott, Rodney J
AU - Scott, Christopher
AU - Seal, Sheila
AU - Seynaeve, Caroline
AU - Shah, Mitul
AU - Sharma, Priyanka
AU - Shen, Chen-Yang
AU - Sheng, Grace
AU - Sherman, Mark E
AU - Shrubsole, Martha J
AU - Shu, Xiao-Ou
AU - Smeets, Ann
AU - Sohn, Christof
AU - Southey, Melissa C
AU - Spinelli, John J
AU - Stegmaier, Christa
AU - Stewart-Brown, Sarah
AU - Stone, Jennifer
AU - Stram, Daniel O
AU - Surowy, Harald
AU - Swerdlow, Anthony
AU - Tamimi, Rulla
AU - Taylor, Jack A
AU - Tengström, Maria
AU - Teo, Soo H
AU - Beth Terry, Mary
AU - Tessier, Daniel C
AU - Thanasitthichai, Somchai
AU - Thöne, Kathrin
AU - Tollenaar, Rob A E M
AU - Tomlinson, Ian
AU - Tong, Ling
AU - Torres, Diana
AU - Truong, Thérèse
AU - Tseng, Chiu-Chen
AU - Tsugane, Shoichiro
AU - Ulmer, Hans-Ulrich
AU - Ursin, Giske
AU - Untch, Michael
AU - Vachon, Celine
AU - van Asperen, Christi J
AU - Van Den Berg, David
AU - van den Ouweland, Ans M W
AU - van der Kolk, Lizet
AU - van der Luijt, Rob B
AU - Vincent, Daniel
AU - Vollenweider, Jason
AU - Waisfisz, Quinten
AU - Wang-Gohrke, Shan
AU - Weinberg, Clarice R
AU - Wendt, Camilla
AU - Whittemore, Alice S
AU - Wildiers, Hans
AU - Willett, Walter
AU - Winqvist, Robert
AU - Wolk, Alicja
AU - Wu, Anna H
AU - Xia, Lucy
AU - Yamaji, Taiki
AU - Yang, Xiaohong R
AU - Har Yip, Cheng
AU - Yoo, Keun-Young
AU - Yu, Jyh-Cherng
AU - Zheng, Wei
AU - Zheng, Ying
AU - Zhu, Bin
AU - Ziogas, Argyrios
AU - Ziv, Elad
AU - Lakhani, Sunil R
AU - Antoniou, Antonis C
AU - Droit, Arnaud
AU - Andrulis, Irene L
AU - Amos, Christopher I
AU - Couch, Fergus J
AU - Pharoah, Paul D P
AU - Chang-Claude, Jenny
AU - Hall, Per
AU - Hunter, David J
AU - Milne, Roger L
AU - García-Closas, Montserrat
AU - Schmidt, Marjanka K
AU - Chanock, Stephen J
AU - Dunning, Alison M
AU - Edwards, Stacey L
AU - Bader, Gary D
AU - Chenevix-Trench, Georgia
AU - Simard, Jacques
AU - Kraft, Peter
AU - Easton, Douglas F
AU - NBCS Collaborators
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.
KW - Journal Article
U2 - 10.1038/nature24284
DO - 10.1038/nature24284
M3 - SCORING: Journal article
C2 - 29059683
VL - 551
SP - 92
EP - 94
JO - NATURE
JF - NATURE
SN - 0028-0836
IS - 7678
ER -