Open AccessAssociation analysis identifies 65 new breast cancer risk loci
Author(s) -
Kyriaki Michailidou,
Sara Lindström,
Joe Dennis,
Jonathan Beesley,
Shirley Hui,
Siddhartha Kar,
Audrey Lemaçon,
Penny Soucy,
Dylan M. Glubb,
Asha Rostamianfar,
Manjeet K. Bolla,
Qin Wang,
Jonathan P. Tyrer,
Ed Dicks,
Andrew Lee,
Zhaoming Wang,
Jamie Allen,
Renske Keeman,
Ursula Eilber,
Juliet D. French,
Xiaohong Chen,
Laura Fachal,
Karen McCue,
Amy E. McCart Reed,
Maya Ghoussaini,
Jason S. Carroll,
Xia Jiang,
Hilary K. Finucane,
Marcia Adams,
Muriel A. Adank,
Habibul Ahsan,
Kristiina Aittomäki,
Hoda AntonCulver,
Natalia Antonenkova,
Volker Arndt,
Kristan J. Aronson,
Banu K. Arun,
Paul L. Auer,
François Bacot,
Myrto Barrdahl,
Caroline Baynes,
Matthias W. Beckmann,
Sabine Behrens,
Javier Benı́tez,
Marina Bermisheva,
Leslie Bernstein,
Carl Blomqvist,
Natalia Bogdanova,
Stig E. Bojesen,
Bernardo Bonanni,
AnneLise BørresenDale,
Judith S. Brand,
Hiltrud Brauch,
Paul Brennan,
Hermann Brenner,
Louise A. Brinton,
Per Broberg,
Ian W. Brock,
Annegien Broeks,
Angela BrooksWilson,
Sara Y. Brucker,
Thomas Brüning,
Barbara Burwinkel,
Katja Butterbach,
Qiuyin Cai,
Hui Cai,
Trinidad Caldés,
Federico Canzian,
Ãngel Carracedo,
Brian D. Carter,
Jose E. Castelao,
Tsun Leung Chan,
TingYuan David Cheng,
Kee Seng Chia,
JiYeob Choi,
Hans Christiansen,
Christine L. Clarke,
Margriet Collée,
Don Conroy,
Emilie CordinaDuverger,
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 dosSantosSilva,
Martine Dumont,
Lorraine Durcan,
Miriam Dwek,
Diana Eccles,
Arif B. Ekici,
A. Heather Eliassen,
Carolina Ellberg,
Mingajeva Elvira,
Christoph Engel,
Mikael Eriksson,
Peter A. Fasching,
Jonine D. Figueroa,
Dieter FleschJanys,
Olivia Fletcher,
Henrik Flyger,
Lin Fritschi,
Valérie Gaborieau,
Marike Gabrielson,
Manuela GagoDominguez,
YuTang Gao,
Susan M. Gapstur,
José Á. García-Sáenz,
Mia M. Gaudet,
V. Georgoulias,
Graham G. Giles,
Gord Glendon,
Mark S. Goldberg,
David E. Goldgar,
Anna GonzálezNeira,
Grethe I.G. Alnæs,
Mervi Grip,
Jacek Gronwald,
Anne Grundy,
Pascal Guénel,
Lothar Haeberle,
Eric Hahnen,
Christopher A. Haiman,
Niclas Håkansson,
Ute Hamann,
Nathalie Hamel,
Susan E. Hankinson,
Patricia Harrington,
Steven N. Hart,
Jaana M. Hartikainen,
Mikael Hartman,
Alexander Hein,
Jane Heyworth,
Belynda Hicks,
Peter Hillemanns,
Do. Ho,
Antoinette Hollestelle,
Maartje J. Hooning,
Robert N. Hoover,
John L. Hopper,
MingFeng Hou,
ChiaNi 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 E. Jones,
Arja JukkolaVuorinen,
Rudolf Kaaks,
Maria Kabisch,
Katarzyna Kaczmarek,
Daehee Kang,
Yoshio Kasuga,
Michael J. Kerin,
Sofia Khan,
Э. К. Хуснутдинова,
Johanna I. Kiiski,
Sung-Won Kim,
Julia A. Knight,
VeliMatti Kosma,
Vessela N. Kristensen,
Ute Krüger,
Ava Kwong,
Diether Lambrechts,
Loı̈c Le Marchand,
Eunjung Lee,
Min Hyuk Lee,
Jong Won Lee,
Chuen Neng Lee,
Flavio Lejbkowicz,
Jingmei Li,
Jenna Lilyquist,
Annika Lindblom,
Jolanta Lissowska,
WingYee Lo,
Sibylle Loibl,
Jirong Long,
Artitaya Lophatana,
Jan Lubiński,
Craig Luccarini,
Michael P. Lux,
Edmond S.K.,
Robert J. MacInnis,
Tom Maishman,
Enes Makalic,
Kathleen E. Malone,
Ivana Maleva Kostovska,
Graham J. Mann,
Siranoush Manoukian,
JoAnn E. Manson,
Sara Margolin,
Shivaani Mariapun,
Marı́a Elena Martı́nez,
Keitaro Matsuo,
Dimitrios Mavroudis,
James McKay,
Catriona McLean,
Hanne MeijersHeijboer,
Alfons Meindl,
Primitiva Menéndez,
Usha Me,
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,
DongYoung Noh,
Børge G. Nordestgaard,
Aaron D. Norman,
Olufunmilayo I. Olopade,
Janet E. Olson,
Håkan Olsson,
Curtis Olswold,
Nick Orr,
V. Shane Pankratz,
Sue K. Park,
TjoungWon ParkSimon,
Rachel Lloyd,
José Ignacio Arias Pérez,
Paolo Peterlongo,
Julian Peto,
KellyAnne Phillips,
Mila Pinchev,
Dijana PlaseskaKaranfilska,
Ross L. Prentice,
Nadège Presneau,
Darya Prokofyeva,
Elizabeth Pugh,
Katri Pylkäs,
Brigitte Rack,
Paolo Radice,
Nazneen Rahman,
Gad Rennert,
Hedy S. Rennert,
Valerie Rhenius,
Atocha Romero,
Jane Romm,
Kathryn J. Ruddy,
Thomas Rüdiger,
Anja Rudolph,
Matthias Ruebner,
Emiel J. Rutgers,
Emmanouil Saloustros,
Dale P. Sandler,
Suleeporn Sangrajrang,
Elinor J. Sawyer,
Daniel F. Schmidt,
Rita K. Schmutzler,
Andreas Schneeweiß,
Minouk J. Schoemaker,
Fredrick R. Schumacher,
Peter Schürmann,
Rodney J. Scott,
Christopher G. Scott,
Sheila Seal,
Caroline Seynaeve,
Mitul Shah,
Priyanka Sharma,
ChenYang Shen,
Grace Sheng,
Mark E. Sherman,
Martha J. Shrubsole,
XiaoOu Shu,
Ann Smeets,
Christof Sohn,
Melissa C. Southey,
John J. Spinelli,
Christa Stegmaier,
Sarah StewartBrown,
Jennifer Stone,
Daniel O. Stram,
Harald Surowy,
Anthony J. Swerdlow,
Rulla M. Tamimi,
Jack A. Taylor,
Maria Tengström,
SooHwang Teo,
Mary Beth Terry,
Daniel C. Tessier,
Somchai Thanasitthichai,
Kathrin Thöne,
Rob A.�E.�M. Tollenaar,
Ian Tomlinson,
Ling Tong,
Diana Torres,
Thérèse Truong,
Chiu-Chen Tseng,
Shoichiro Tsugane,
Hans-Ulrich Ulmer,
Giske Ursin,
Michael Untch,
Celine M. Vachon,
Christi J. van Asperen,
David Van Den Berg,
Ans M.W. van den Ouweland,
Lizet van der Kolk,
Rob B. van der Luijt,
Daniel Vincent,
Jason Vollenweider,
Quinten Waisfisz,
Shan WangGohrke,
Clarice R. Weinberg,
Camilla Wendt,
Alice S. Whittemore,
Hans Wildiers,
Walter C. Willett,
Robert Winqvist,
Alicja Wolk,
Anna H. Wu,
Lucy Xia,
Taiki Yamaji,
Xiaohong R. Yang,
Cheng Har Yip,
Keun-Young Yoo,
JyhCherng Yu,
Wei Zheng,
Ying Zheng,
Bin Zhu,
Argyrios Ziogas,
Elad Ziv,
Sunil R. Lakhani,
Antonis C. Antoniou,
Arnaud Droit,
Irene L. Andrulis,
Christopher I. Amos,
Fergus J. Couch,
Paul D.P. Pharoah,
Jenny ChangClaude,
Per Hall,
David J. Hunter,
Roger L. Milne,
Montserrat GarcíaClosas,
Marjanka K. Schmidt,
Stephen J. Chanock,
Alison M. Dunning,
Stacey L. Edwards,
Gary D. Bader,
Georgia ChenevixTrench,
Jacques Simard,
Peter Kraft,
Douglas F. Easton
Publication year - 2017
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/nature24284
Subject(s) - breast cancer , single nucleotide polymorphism , genome wide association study , genetic association , genetics , biology , case control study , snp , genetic predisposition , cancer , oncology , medicine , gene , genotype
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.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom