Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

Hatef Darabi; Jonathan Beesley; Arnaud Droit; Siddhartha Kar; Silje Nord; Mahdi Moradi Marjaneh; Penny Soucy; Kyriaki Michailidou; Maya Ghoussaini; Hanna Fues Wahl; Manjeet K. Bolla; Qin Wang; Joe Dennis; M. Rosario Alonso; Irene L. Andrulis; Hoda Anton-Culver; Volker Arndt; Matthias W. Beckmann; Javier Benitez; Natalia V. Bogdanova; Stig E. Bojesen; Hiltrud Brauch; Hermann Brenner; Annegien Broeks; Thomas Brüning; Barbara Burwinkel; Jenny Chang-Claude; Ji Yeob Choi; Don M. Conroy; Fergus J. Couch; Angela Cox; Simon S. Cross; Kamila Czene; Peter Devilee; Thilo Dörk; Douglas F. Easton; Peter A. Fasching; Jonine Figueroa; Olivia Fletcher; Henrik Flyger; Eva Galle; Montserrat García-Closas; Graham G. Giles; Mark S. Goldberg; Anna González-Neira; Pascal Guénel; Christopher A. Haiman; Emily Hallberg; Ute Hamann; Mikael Hartman; Antoinette Hollestelle; John L. Hopper; Hidemi Ito; Anna Jakubowska; Nichola Johnson; Daehee Kang; Sofia Khan; Veli Matti Kosma; Mieke Kriege; Vessela Kristensen; Diether Lambrechts; Loic Le Marchand; Soo Chin Lee; Annika Lindblom; Artitaya Lophatananon; Jan Lubinski; Arto Mannermaa; Siranoush Manoukian; Sara Margolin; Keitaro Matsuo; Rebecca Mayes; James McKay; Alfons Meindl; Roger L. Milne; Kenneth Muir; Susan L. Neuhausen; Heli Nevanlinna; Curtis Olswold; Nick Orr; Paolo Peterlongo; Guillermo Pita; Katri Pylkäs; Anja Rudolph; Suleeporn Sangrajrang; Elinor J. Sawyer; Marjanka K. Schmidt; Rita K. Schmutzler; Caroline Seynaeve; Mitul Shah; Chen Yang Shen; Xiao Ou Shu; Melissa C. Southey; Daniel O. Stram; Harald Surowy; Anthony Swerdlow; Soo H. Teo; Daniel C. Tessier; Ian Tomlinson; Diana Torres; Thérèse Truong; Celine M. Vachon; Daniel Vincent; Robert Winqvist; Anna H. Wu; Pei Ei Wu; Cheng Har Yip; Wei Zheng; Paul D.P. Pharoah; Per Hall; Stacey L. Edwards; Jacques Simard; Juliet D. French; Georgia Chenevix-Trench; Alison M. Dunning

doi:10.1038/srep32512

Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

Hatef Darabi
, Jonathan Beesley
, Arnaud Droit
, Siddhartha Kar
, Silje Nord
, Mahdi Moradi Marjaneh
, Penny Soucy
, Kyriaki Michailidou
, Maya Ghoussaini
, Hanna Fues Wahl
, Manjeet K. Bolla
, Qin Wang
, Joe Dennis
, M. Rosario Alonso
, Irene L. Andrulis
, Hoda Anton-Culver
, Volker Arndt
, Matthias W. Beckmann
, Javier Benitez
, Natalia V. Bogdanova

Stig E. Bojesen, Hiltrud Brauch, Hermann Brenner, Annegien Broeks, Thomas Brüning, Barbara Burwinkel, Jenny Chang-Claude, Ji Yeob Choi, Don M. Conroy, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Peter Devilee, Thilo Dörk, Douglas F. Easton, Peter A. Fasching, Jonine Figueroa, Olivia Fletcher, Henrik Flyger, Eva Galle, Montserrat García-Closas, Graham G. Giles, Mark S. Goldberg, Anna González-Neira, Pascal Guénel, Christopher A. Haiman, Emily Hallberg, Ute Hamann, Mikael Hartman, Antoinette Hollestelle, John L. Hopper, Hidemi Ito, Anna Jakubowska, Nichola Johnson, Daehee Kang, Sofia Khan, Veli Matti Kosma, Mieke Kriege, Vessela Kristensen, Diether Lambrechts, Loic Le Marchand, Soo Chin Lee, Annika Lindblom, Artitaya Lophatananon, Jan Lubinski, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Keitaro Matsuo, Rebecca Mayes, James McKay, Alfons Meindl, Roger L. Milne, Kenneth Muir, Susan L. Neuhausen, Heli Nevanlinna, Curtis Olswold, Nick Orr, Paolo Peterlongo, Guillermo Pita, Katri Pylkäs, Anja Rudolph, Suleeporn Sangrajrang, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Caroline Seynaeve, Mitul Shah, Chen Yang Shen, Xiao Ou Shu, Melissa C. Southey, Daniel O. Stram, Harald Surowy, Anthony Swerdlow, Soo H. Teo, Daniel C. Tessier, Ian Tomlinson, Diana Torres, Thérèse Truong, Celine M. Vachon, Daniel Vincent, Robert Winqvist, Anna H. Wu, Pei Ei Wu, Cheng Har Yip, Wei Zheng, Paul D.P. Pharoah, Per Hall, Stacey L. Edwards, Jacques Simard, Juliet D. French, Georgia Chenevix-Trench, Alison M. Dunning

Institute of Human Genetics

Karolinska Institutet
Queensland Institute of Medical Research
Research Center
University of Cambridge
University of Oslo
Cyprus Institute of Neurology and Genetics
Centro de Investigación en Red de Enfermedades Raras
University of Toronto
University of California, Irvine
German Cancer Research Center
Friedrich-Alexander University Erlangen-Nürnberg
Centre for Biomedical Research on Rare Diseases (CIBERER)
Hannover Medical School
Copenhagen University Hospital – Herlev and Gentofte
University of Copenhagen
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
University of Tübingen
Antoni van Leeuwenhoek Hospital
Ruhr University Bochum
Heidelberg University
University of Hamburg
Seoul National University
Mayo Clinic Rochester, MN
University of Sheffield
Leiden University
University of California at Los Angeles
University of Edinburgh
National Cancer Institute (NCI)
Institute of Cancer Research
Vesalius Research Center
KU Leuven
Cancer Council Victoria
Centre for Epidemiology and Biostatistics
McGill University
McGill University Health Centre, Royal Victoria Hospital
Occupational and Social Determinants of Health
Keck School of Medicine of USC
National University of Singapore
MOH Holdings Pte Ltd.
Erasmus MC Cancer Institute
Aichi Cancer Center Hospital and Research Institute
Pomeranian Medical University in Szczecin
Helsinki University Hospital
University of Eastern Finland
University of Hawaii Cancer Center
University of Warwick
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
International Agency for Research on Cancer
Technical University of Munich
University of Manchester
City of Hope National Med Center
FIRC Institute of Molecular Oncology
University of Oulu
Northern Finland Laboratory Centre NordLab
The National Cancer Institute
Guy’s Hospital
University of Cologne
Universität zu Köln
Academia Sinica - Institute of Biomedical Sciences
Vanderbilt University
University of Melbourne
Sime Darby Medical Centre
University of Malaya
University of Oxford

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

18 Scopus citations

Abstract

Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10¹⁵)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10⁰⁹, r² = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10¹¹, r² = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

Original language	English
Article number	32512
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep32512
State	Published - 07 Sep 2016

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Darabi, H., Beesley, J., Droit, A., Kar, S., Nord, S., Marjaneh, M. M., Soucy, P., Michailidou, K., Ghoussaini, M., Wahl, H. F., Bolla, M. K., Wang, Q., Dennis, J., Alonso, M. R., Andrulis, I. L., Anton-Culver, H., Arndt, V., Beckmann, M. W., Benitez, J., ... Dunning, A. M. (2016). Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs). Scientific Reports, 6, Article 32512. https://doi.org/10.1038/srep32512

@article{0ca657e887da4d7397bb9d104a6fecb0,

title = "Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)",

abstract = "Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 1015)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 1009, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 1011, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.",

author = "Hatef Darabi and Jonathan Beesley and Arnaud Droit and Siddhartha Kar and Silje Nord and Marjaneh, \{Mahdi Moradi\} and Penny Soucy and Kyriaki Michailidou and Maya Ghoussaini and Wahl, \{Hanna Fues\} and Bolla, \{Manjeet K.\} and Qin Wang and Joe Dennis and Alonso, \{M. Rosario\} and Andrulis, \{Irene L.\} and Hoda Anton-Culver and Volker Arndt and Beckmann, \{Matthias W.\} and Javier Benitez and Bogdanova, \{Natalia V.\} and Bojesen, \{Stig E.\} and Hiltrud Brauch and Hermann Brenner and Annegien Broeks and Thomas Br{\"u}ning and Barbara Burwinkel and Jenny Chang-Claude and Choi, \{Ji Yeob\} and Conroy, \{Don M.\} and Couch, \{Fergus J.\} and Angela Cox and Cross, \{Simon S.\} and Kamila Czene and Peter Devilee and Thilo D{\"o}rk and Easton, \{Douglas F.\} and Fasching, \{Peter A.\} and Jonine Figueroa and Olivia Fletcher and Henrik Flyger and Eva Galle and Montserrat Garc{\'i}a-Closas and Giles, \{Graham G.\} and Goldberg, \{Mark S.\} and Anna Gonz{\'a}lez-Neira and Pascal Gu{\'e}nel and Haiman, \{Christopher A.\} and Emily Hallberg and Ute Hamann and Mikael Hartman and Antoinette Hollestelle and Hopper, \{John L.\} and Hidemi Ito and Anna Jakubowska and Nichola Johnson and Daehee Kang and Sofia Khan and Kosma, \{Veli Matti\} and Mieke Kriege and Vessela Kristensen and Diether Lambrechts and \{Le Marchand\}, Loic and Lee, \{Soo Chin\} and Annika Lindblom and Artitaya Lophatananon and Jan Lubinski and Arto Mannermaa and Siranoush Manoukian and Sara Margolin and Keitaro Matsuo and Rebecca Mayes and James McKay and Alfons Meindl and Milne, \{Roger L.\} and Kenneth Muir and Neuhausen, \{Susan L.\} and Heli Nevanlinna and Curtis Olswold and Nick Orr and Paolo Peterlongo and Guillermo Pita and Katri Pylk{\"a}s and Anja Rudolph and Suleeporn Sangrajrang and Sawyer, \{Elinor J.\} and Schmidt, \{Marjanka K.\} and Schmutzler, \{Rita K.\} and Caroline Seynaeve and Mitul Shah and Shen, \{Chen Yang\} and Shu, \{Xiao Ou\} and Southey, \{Melissa C.\} and Stram, \{Daniel O.\} and Harald Surowy and Anthony Swerdlow and Teo, \{Soo H.\} and Tessier, \{Daniel C.\} and Ian Tomlinson and Diana Torres and Th{\'e}r{\`e}se Truong and Vachon, \{Celine M.\} and Daniel Vincent and Robert Winqvist and Wu, \{Anna H.\} and Wu, \{Pei Ei\} and Yip, \{Cheng Har\} and Wei Zheng and Pharoah, \{Paul D.P.\} and Per Hall and Edwards, \{Stacey L.\} and Jacques Simard and French, \{Juliet D.\} and Georgia Chenevix-Trench and Dunning, \{Alison M.\}",

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

month = sep,

day = "7",

doi = "10.1038/srep32512",

language = "English",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Research",

}

Darabi, H, Beesley, J, Droit, A, Kar, S, Nord, S, Marjaneh, MM, Soucy, P, Michailidou, K, Ghoussaini, M, Wahl, HF, Bolla, MK, Wang, Q, Dennis, J, Alonso, MR, Andrulis, IL, Anton-Culver, H, Arndt, V, Beckmann, MW, Benitez, J, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Broeks, A, Brüning, T, Burwinkel, B, Chang-Claude, J, Choi, JY, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Devilee, P, Dörk, T, Easton, DF, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Galle, E, García-Closas, M, Giles, GG, Goldberg, MS, González-Neira, A, Guénel, P, Haiman, CA, Hallberg, E, Hamann, U, Hartman, M, Hollestelle, A, Hopper, JL, Ito, H, Jakubowska, A, Johnson, N, Kang, D, Khan, S, Kosma, VM, Kriege, M, Kristensen, V, Lambrechts, D, Le Marchand, L, Lee, SC, Lindblom, A, Lophatananon, A, Lubinski, J, Mannermaa, A, Manoukian, S, Margolin, S, Matsuo, K, Mayes, R, McKay, J, Meindl, A, Milne, RL, Muir, K, Neuhausen, SL, Nevanlinna, H, Olswold, C, Orr, N, Peterlongo, P, Pita, G, Pylkäs, K, Rudolph, A, Sangrajrang, S, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Seynaeve, C, Shah, M, Shen, CY, Shu, XO, Southey, MC, Stram, DO, Surowy, H, Swerdlow, A, Teo, SH, Tessier, DC, Tomlinson, I, Torres, D, Truong, T, Vachon, CM, Vincent, D, Winqvist, R, Wu, AH, Wu, PE, Yip, CH, Zheng, W, Pharoah, PDP, Hall, P, Edwards, SL, Simard, J, French, JD, Chenevix-Trench, G & Dunning, AM 2016, 'Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)', Scientific Reports, vol. 6, 32512. https://doi.org/10.1038/srep32512

TY - JOUR

T1 - Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

AU - Darabi, Hatef

AU - Beesley, Jonathan

AU - Droit, Arnaud

AU - Kar, Siddhartha

AU - Nord, Silje

AU - Marjaneh, Mahdi Moradi

AU - Soucy, Penny

AU - Michailidou, Kyriaki

AU - Ghoussaini, Maya

AU - Wahl, Hanna Fues

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Dennis, Joe

AU - Alonso, M. Rosario

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Arndt, Volker

AU - Beckmann, Matthias W.

AU - Benitez, Javier

AU - Bogdanova, Natalia V.

AU - Bojesen, Stig E.

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Broeks, Annegien

AU - Brüning, Thomas

AU - Burwinkel, Barbara

AU - Chang-Claude, Jenny

AU - Choi, Ji Yeob

AU - Conroy, Don M.

AU - Couch, Fergus J.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Czene, Kamila

AU - Devilee, Peter

AU - Dörk, Thilo

AU - Easton, Douglas F.

AU - Fasching, Peter A.

AU - Figueroa, Jonine

AU - Fletcher, Olivia

AU - Flyger, Henrik

AU - Galle, Eva

AU - García-Closas, Montserrat

AU - Giles, Graham G.

AU - Goldberg, Mark S.

AU - González-Neira, Anna

AU - Guénel, Pascal

AU - Haiman, Christopher A.

AU - Hallberg, Emily

AU - Hamann, Ute

AU - Hartman, Mikael

AU - Hollestelle, Antoinette

AU - Hopper, John L.

AU - Ito, Hidemi

AU - Jakubowska, Anna

AU - Johnson, Nichola

AU - Kang, Daehee

AU - Khan, Sofia

AU - Kosma, Veli Matti

AU - Kriege, Mieke

AU - Kristensen, Vessela

AU - Lambrechts, Diether

AU - Le Marchand, Loic

AU - Lee, Soo Chin

AU - Lindblom, Annika

AU - Lophatananon, Artitaya

AU - Lubinski, Jan

AU - Mannermaa, Arto

AU - Manoukian, Siranoush

AU - Margolin, Sara

AU - Matsuo, Keitaro

AU - Mayes, Rebecca

AU - McKay, James

AU - Meindl, Alfons

AU - Milne, Roger L.

AU - Muir, Kenneth

AU - Neuhausen, Susan L.

AU - Nevanlinna, Heli

AU - Olswold, Curtis

AU - Orr, Nick

AU - Peterlongo, Paolo

AU - Pita, Guillermo

AU - Pylkäs, Katri

AU - Rudolph, Anja

AU - Sangrajrang, Suleeporn

AU - Sawyer, Elinor J.

AU - Schmidt, Marjanka K.

AU - Schmutzler, Rita K.

AU - Seynaeve, Caroline

AU - Shah, Mitul

AU - Shen, Chen Yang

AU - Shu, Xiao Ou

AU - Southey, Melissa C.

AU - Stram, Daniel O.

AU - Surowy, Harald

AU - Swerdlow, Anthony

AU - Teo, Soo H.

AU - Tessier, Daniel C.

AU - Tomlinson, Ian

AU - Torres, Diana

AU - Truong, Thérèse

AU - Vachon, Celine M.

AU - Vincent, Daniel

AU - Winqvist, Robert

AU - Wu, Anna H.

AU - Wu, Pei Ei

AU - Yip, Cheng Har

AU - Zheng, Wei

AU - Pharoah, Paul D.P.

AU - Hall, Per

AU - Edwards, Stacey L.

AU - Simard, Jacques

AU - French, Juliet D.

AU - Chenevix-Trench, Georgia

AU - Dunning, Alison M.

PY - 2016/9/7

Y1 - 2016/9/7

N2 - Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 1015)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 1009, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 1011, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

AB - Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 1015)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 1009, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 1011, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

UR - https://www.scopus.com/pages/publications/84986253509

U2 - 10.1038/srep32512

DO - 10.1038/srep32512

M3 - Article

C2 - 27600471

AN - SCOPUS:84986253509

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 32512

ER -

Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

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