Publication

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Zeng, C., Guo, X., Long, J., Kuchenbaecker, K. B., Droit, A., Michailidou, K., Ghoussaini, M., Kar, S., Freeman, A., Hopper, J. L., Milne, R. L., Bolla, M. K., Wang, Q., Dennis, J., Agata, S., Ahmed, S., Aittomaki, K., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Arason, A., Arndt, V., Arun, B. K., Arver, B., Bacot, F., Barrowdale, D., Baynes, C., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Blomqvist, C., Blot, W. J., Bogdanova, N. V., Bojesen, S. E., Bonanni, B., Borresen-Dale, A-L., Brand, J. S., Brauch, H., Brennan, P., Brenner, H., Broeks, A., Bruening, T., Burwinkel, B., Buys, S. S., Cai, Q., Caldes, T., Campbell, I., EMBRACE, GEMO Study Collaborators, HEBON, kConFab & AOCS Investigators, 21-Jun-2016, In : Breast cancer research. 18, 64, 21 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Zeng, C., Guo, X., Long, J., Kuchenbaecker, K. B., Droit, A., Michailidou, K., Ghoussaini, M., Kar, S., Freeman, A., Hopper, J. L., Milne, R. L., Bolla, M. K., Wang, Q., Dennis, J., Agata, S., Ahmed, S., Aittomaki, K., Andrulis, I. L., Anton-Culver, H., ... AOCS Investigators (2016). Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. Breast cancer research, 18(64). https://doi.org/10.1186/s13058-016-0718-0

Author

Zeng, Chenjie ; Guo, Xingyi ; Long, Jirong ; Kuchenbaecker, Karoline B. ; Droit, Arnaud ; Michailidou, Kyriaki ; Ghoussaini, Maya ; Kar, Siddhartha ; Freeman, Adam ; Hopper, John L. ; Milne, Roger L. ; Bolla, Manjeet K. ; Wang, Qin ; Dennis, Joe ; Agata, Simona ; Ahmed, Shahana ; Aittomaki, Kristiina ; Andrulis, Irene L. ; Anton-Culver, Hoda ; Antonenkova, Natalia N. ; Arason, Adalgeir ; Arndt, Volker ; Arun, Banu K. ; Arver, Brita ; Bacot, Francois ; Barrowdale, Daniel ; Baynes, Caroline ; Beeghly-Fadiel, Alicia ; Benitez, Javier ; Bermisheva, Marina ; Blomqvist, Carl ; Blot, William J. ; Bogdanova, Natalia V. ; Bojesen, Stig E. ; Bonanni, Bernardo ; Borresen-Dale, Anne-Lise ; Brand, Judith S. ; Brauch, Hiltrud ; Brennan, Paul ; Brenner, Hermann ; Broeks, Annegien ; Bruening, Thomas ; Burwinkel, Barbara ; Buys, Saundra S. ; Cai, Qiuyin ; Caldes, Trinidad ; Campbell, Ian ; EMBRACE ; GEMO Study Collaborators ; HEBON ; kConFab ; AOCS Investigators. / Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. In: Breast cancer research. 2016 ; Vol. 18, No. 64.

Harvard

Zeng, C, Guo, X, Long, J, Kuchenbaecker, KB, Droit, A, Michailidou, K, Ghoussaini, M, Kar, S, Freeman, A, Hopper, JL, Milne, RL, Bolla, MK, Wang, Q, Dennis, J, Agata, S, Ahmed, S, Aittomaki, K, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arason, A, Arndt, V, Arun, BK, Arver, B, Bacot, F, Barrowdale, D, Baynes, C, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Blomqvist, C, Blot, WJ, Bogdanova, NV, Bojesen, SE, Bonanni, B, Borresen-Dale, A-L, Brand, JS, Brauch, H, Brennan, P, Brenner, H, Broeks, A, Bruening, T, Burwinkel, B, Buys, SS, Cai, Q, Caldes, T, Campbell, I, EMBRACE, GEMO Study Collaborators, HEBON, kConFab & AOCS Investigators 2016, 'Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus', Breast cancer research, vol. 18, no. 64. https://doi.org/10.1186/s13058-016-0718-0

Standard

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. / Zeng, Chenjie; Guo, Xingyi; Long, Jirong; Kuchenbaecker, Karoline B.; Droit, Arnaud; Michailidou, Kyriaki; Ghoussaini, Maya; Kar, Siddhartha; Freeman, Adam; Hopper, John L.; Milne, Roger L.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Agata, Simona; Ahmed, Shahana; Aittomaki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arason, Adalgeir; Arndt, Volker; Arun, Banu K.; Arver, Brita; Bacot, Francois; Barrowdale, Daniel; Baynes, Caroline; Beeghly-Fadiel, Alicia; Benitez, Javier; Bermisheva, Marina; Blomqvist, Carl; Blot, William J.; Bogdanova, Natalia V.; Bojesen, Stig E.; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S.; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Broeks, Annegien; Bruening, Thomas; Burwinkel, Barbara; Buys, Saundra S.; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; EMBRACE; GEMO Study Collaborators; HEBON; kConFab; AOCS Investigators.

In: Breast cancer research, Vol. 18, No. 64, 21.06.2016.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Zeng C, Guo X, Long J, Kuchenbaecker KB, Droit A, Michailidou K et al. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. Breast cancer research. 2016 Jun 21;18(64). https://doi.org/10.1186/s13058-016-0718-0


BibTeX

@article{782d01ead64947409dd86a71ecbae286,
title = "Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus",
abstract = "Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P <0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P <0.05.Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.",
keywords = "Fine-scale mapping, Genetic risk factor, PTHLH, CCDC91, Breast cancer, BRAC1 mutation carriers, HORMONE-RELATED PROTEIN, GENOME-WIDE ASSOCIATION, BRCA2 MUTATION CARRIERS, SUSCEPTIBILITY LOCI, GENETIC MODIFIERS, OVARIAN-CANCER, LOCALIZATION, METASTASIS, EXPRESSION, ENHANCERS",
author = "Chenjie Zeng and Xingyi Guo and Jirong Long and Kuchenbaecker, {Karoline B.} and Arnaud Droit and Kyriaki Michailidou and Maya Ghoussaini and Siddhartha Kar and Adam Freeman and Hopper, {John L.} and Milne, {Roger L.} and Bolla, {Manjeet K.} and Qin Wang and Joe Dennis and Simona Agata and Shahana Ahmed and Kristiina Aittomaki and Andrulis, {Irene L.} and Hoda Anton-Culver and Antonenkova, {Natalia N.} and Adalgeir Arason and Volker Arndt and Arun, {Banu K.} and Brita Arver and Francois Bacot and Daniel Barrowdale and Caroline Baynes and Alicia Beeghly-Fadiel and Javier Benitez and Marina Bermisheva and Carl Blomqvist and Blot, {William J.} and Bogdanova, {Natalia V.} and Bojesen, {Stig E.} and Bernardo Bonanni and Anne-Lise Borresen-Dale and Brand, {Judith S.} and Hiltrud Brauch and Paul Brennan and Hermann Brenner and Annegien Broeks and Thomas Bruening and Barbara Burwinkel and Buys, {Saundra S.} and Qiuyin Cai and Trinidad Caldes and Ian Campbell and EMBRACE and {GEMO Study Collaborators} and HEBON and kConFab and {AOCS Investigators} and Jakobus Ligtenberg and Jan Oosterwijk and {van der Hout}, Annemarie",
year = "2016",
month = jun,
day = "21",
doi = "10.1186/s13058-016-0718-0",
language = "English",
volume = "18",
journal = "Breast cancer research",
issn = "1465-5411",
publisher = "BioMed Central Ltd.",
number = "64",

}

RIS

TY - JOUR

T1 - Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

AU - Zeng, Chenjie

AU - Guo, Xingyi

AU - Long, Jirong

AU - Kuchenbaecker, Karoline B.

AU - Droit, Arnaud

AU - Michailidou, Kyriaki

AU - Ghoussaini, Maya

AU - Kar, Siddhartha

AU - Freeman, Adam

AU - Hopper, John L.

AU - Milne, Roger L.

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Dennis, Joe

AU - Agata, Simona

AU - Ahmed, Shahana

AU - Aittomaki, Kristiina

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N.

AU - Arason, Adalgeir

AU - Arndt, Volker

AU - Arun, Banu K.

AU - Arver, Brita

AU - Bacot, Francois

AU - Barrowdale, Daniel

AU - Baynes, Caroline

AU - Beeghly-Fadiel, Alicia

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Blomqvist, Carl

AU - Blot, William J.

AU - Bogdanova, Natalia V.

AU - Bojesen, Stig E.

AU - Bonanni, Bernardo

AU - Borresen-Dale, Anne-Lise

AU - Brand, Judith S.

AU - Brauch, Hiltrud

AU - Brennan, Paul

AU - Brenner, Hermann

AU - Broeks, Annegien

AU - Bruening, Thomas

AU - Burwinkel, Barbara

AU - Buys, Saundra S.

AU - Cai, Qiuyin

AU - Caldes, Trinidad

AU - Campbell, Ian

AU - EMBRACE

AU - GEMO Study Collaborators

AU - HEBON

AU - kConFab

AU - AOCS Investigators

AU - Ligtenberg, Jakobus

AU - Oosterwijk, Jan

AU - van der Hout, Annemarie

PY - 2016/6/21

Y1 - 2016/6/21

N2 - Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P <0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P <0.05.Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.

AB - Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P <0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P <0.05.Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.

KW - Fine-scale mapping

KW - Genetic risk factor

KW - PTHLH

KW - CCDC91

KW - Breast cancer

KW - BRAC1 mutation carriers

KW - HORMONE-RELATED PROTEIN

KW - GENOME-WIDE ASSOCIATION

KW - BRCA2 MUTATION CARRIERS

KW - SUSCEPTIBILITY LOCI

KW - GENETIC MODIFIERS

KW - OVARIAN-CANCER

KW - LOCALIZATION

KW - METASTASIS

KW - EXPRESSION

KW - ENHANCERS

U2 - 10.1186/s13058-016-0718-0

DO - 10.1186/s13058-016-0718-0

M3 - Article

VL - 18

JO - Breast cancer research

JF - Breast cancer research

SN - 1465-5411

IS - 64

ER -

ID: 49401786