Dennis, Joe, Tyrer, Jonathan P., Walker, Logan C., Michailidou, Kyriaki ORCID: 0000-0001-7065-1237, Dorling, Leila, Bolla, Manjeet K., Wang, Qin ORCID: 0000-0002-9139-0627, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia, V, Bojesen, Stig E., Brenner, Hermann ORCID: 0000-0002-6129-1572, Castelao, Jose E., Chang-Claude, Jenny, Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Couch, Fergus J., Cox, Angela ORCID: 0000-0002-5138-1099, Cross, Simon S., Czene, Kamila, Devilee, Peter, Dork, Thilo, Dossus, Laure, Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine ORCID: 0000-0002-5100-623X, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike ORCID: 0000-0002-3171-1556, Gago-Dominguez, Manuela, Garcia-Closas, Montserrat ORCID: 0000-0003-1033-2650, Giles, Graham G., Gonzalez-Neira, Anna, Guenel, Pascal ORCID: 0000-0002-8359-518X, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Howell, Anthony, Jager, Agnes, Jakubowska, Anna, John, Esther M., Johnson, Nichola, Jones, Michael E., Jung, Audrey ORCID: 0000-0003-0875-6673, Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Kosma, Veli-Matti, Koutros, Stella ORCID: 0000-0001-5294-5485, Kraft, Peter, Kristensen, Vessela N., Kubelka-Sabit, Katerina, Kurian, Allison W., Lacey, James, V, Lambrechts, Diether ORCID: 0000-0002-3429-302X, Larson, Nicole L., Linet, Martha, Ogrodniczak, Alicja, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara ORCID: 0000-0002-5526-5570, Mavroudis, Dimitrios, Milne, Roger L., Muranen, Taru A., Murphy, Rachel A., Nevanlinna, Heli, Olson, Janet E., Olsson, Hakan, Park-Simon, Tjoung-Won, Perou, Charles M., Peterlongo, Paolo ORCID: 0000-0001-6951-6855, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad ORCID: 0000-0002-8512-068X, Saloustros, Emmanouil ORCID: 0000-0002-0485-0120, Sandler, Dale P., Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Shibli, Rana, Smeets, Ann, Soucy, Penny, Southey, Melissa C., Swerdlow, Anthony J., Tamimi, Rulla M., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth ORCID: 0000-0002-4106-5033, Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Ziogas, Argyrios, Simard, Jacques, Dunning, Alison M., Pharoah, Paul D. P. and Easton, Douglas F. (2022). Rare germline copy number variants (CNVs) and breast cancer risk. Commun. Biol., 5 (1). BERLIN: NATURE PORTFOLIO. ISSN 2399-3642

Full text not available from this repository.

Abstract

Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance. Dennis et al. investigate potential breast cancer associations with rare germline copy number variants (CNVs) by conducting a genome-wide analysis in a large breast cancer case-control dataset. The authors detected associations with exonic deletions in established breast cancer susceptibility genes and suggestive associations for a number of non-coding CNVs.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dennis, JoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tyrer, Jonathan P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walker, Logan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michailidou, KyriakiUNSPECIFIEDorcid.org/0000-0001-7065-1237UNSPECIFIED
Dorling, LeilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolla, Manjeet K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, QinUNSPECIFIEDorcid.org/0000-0002-9139-0627UNSPECIFIED
Ahearn, Thomas U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anton-Culver, HodaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antonenkova, Natalia N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arndt, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aronson, Kristan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freeman, Laura E. BeaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beckmann, Matthias W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Behrens, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benitez, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bermisheva, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bogdanova, Natalia, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bojesen, Stig E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brenner, HermannUNSPECIFIEDorcid.org/0000-0002-6129-1572UNSPECIFIED
Castelao, Jose E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chang-Claude, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clarke, Christine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collee, J. MargrietUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cox, AngelaUNSPECIFIEDorcid.org/0000-0002-5138-1099UNSPECIFIED
Cross, Simon S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czene, KamilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devilee, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dork, ThiloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dossus, LaureUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eliassen, A. HeatherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eriksson, MikaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evans, D. GarethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fasching, Peter A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Figueroa, JonineUNSPECIFIEDorcid.org/0000-0002-5100-623XUNSPECIFIED
Fletcher, OliviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flyger, HenrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fritschi, LinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabrielson, MarikeUNSPECIFIEDorcid.org/0000-0002-3171-1556UNSPECIFIED
Gago-Dominguez, ManuelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Closas, MontserratUNSPECIFIEDorcid.org/0000-0003-1033-2650UNSPECIFIED
Giles, Graham G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez-Neira, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenel, PascalUNSPECIFIEDorcid.org/0000-0002-8359-518XUNSPECIFIED
Hahnen, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haiman, Christopher A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hall, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hollestelle, AntoinetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoppe, ReinerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hopper, John L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Howell, AnthonyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jager, AgnesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jakubowska, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
John, Esther M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, NicholaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jones, Michael E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jung, AudreyUNSPECIFIEDorcid.org/0000-0003-0875-6673UNSPECIFIED
Kaaks, RudolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keeman, RenskeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khusnutdinova, ElzaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kitahara, Cari M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ko, Yon-DschunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kosma, Veli-MattiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koutros, StellaUNSPECIFIEDorcid.org/0000-0001-5294-5485UNSPECIFIED
Kraft, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kristensen, Vessela N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kubelka-Sabit, KaterinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurian, Allison W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lacey, James, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lambrechts, DietherUNSPECIFIEDorcid.org/0000-0002-3429-302XUNSPECIFIED
Larson, Nicole L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linet, MarthaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ogrodniczak, AlicjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mannermaa, ArtoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manoukian, SiranoushUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Margolin, SaraUNSPECIFIEDorcid.org/0000-0002-5526-5570UNSPECIFIED
Mavroudis, DimitriosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milne, Roger L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muranen, Taru A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murphy, Rachel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nevanlinna, HeliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olson, Janet E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olsson, HakanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park-Simon, Tjoung-WonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perou, Charles M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peterlongo, PaoloUNSPECIFIEDorcid.org/0000-0001-6951-6855UNSPECIFIED
Plaseska-Karanfilska, DijanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pylkas, KatriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rennert, GadUNSPECIFIEDorcid.org/0000-0002-8512-068XUNSPECIFIED
Saloustros, EmmanouilUNSPECIFIEDorcid.org/0000-0002-0485-0120UNSPECIFIED
Sandler, Dale P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sawyer, Elinor J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, Marjanka K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shibli, RanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smeets, AnnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soucy, PennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Southey, Melissa C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Swerdlow, Anthony J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tamimi, Rulla M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taylor, Jack A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teras, Lauren R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Terry, Mary BethUNSPECIFIEDorcid.org/0000-0002-4106-5033UNSPECIFIED
Tomlinson, IanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Troester, Melissa A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Truong, ThereseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vachon, Celine M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wendt, CamillaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winqvist, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolk, AlicjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, Xiaohong R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zheng, WeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziogas, ArgyriosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simard, JacquesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dunning, Alison M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pharoah, Paul D. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-699592
DOI: 10.1038/s42003-021-02990-6
Journal or Publication Title: Commun. Biol.
Volume: 5
Number: 1
Date: 2022
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 2399-3642
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
STRUCTURAL VARIATION; ASSOCIATION; DELETION; LOCUS; MUTATIONS; GENES; BRCA1; RUNX2Multiple languages
Biology; Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69959

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