Capture Hi-C identifies putative target genes at 33 breast cancer risk loci

被引：74

作者：

Baxter, Joseph S. ^{[1
]}

Leavy, Olivia C. ^{[2
,3
]}

Dryden, Nicola H. ^{[1
]}

Maguire, Sarah ^{[1
]}

Johnson, Nichola ^{[1
]}

Fedele, Vita ^{[1
]}

Simigdala, Nikiana ^{[1
]}

Martin, Lesley-Ann ^{[1
]}

Andrews, Simon ^{[4
]}

Wingett, Steven W. ^{[4
]}

Assiotis, Ioannis ^{[5
]}

Fenwick, Kerry ^{[5
]}

Chauhan, Ritika ^{[1
]}

Rust, Alistair G. ^{[1
]}

Orr, Nick ^{[1
]}

Dudbridge, Frank ^{[2
,3
]}

Haider, Syed ^{[1
]}

Fletcher, Olivia ^{[1
]}

机构：

[1] Inst Canc Res, Breast Canc Now Toby Robins Res Ctr, London SW3 6JB, England

[2] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1E 7HT, England

[3] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England

[4] Babraham Inst, Bioinformat Grp, Cambridge CB22 3AT, England

[5] Inst Canc Res, Tumour Profiling Unit, London SW3 6JB, England

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

欧盟地平线“2020”;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; FUNCTIONAL VARIANTS; CONFER SUSCEPTIBILITY; COMMON VARIANTS; REVEALS; ALLELES; ARCHITECTURE; EXPRESSION; PRINCIPLES;

D O I：

10.1038/s41467-018-03411-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genome-wide association studies (GWAS) have identified approximately 100 breast cancer risk loci. Translating these findings into a greater understanding of the mechanisms that influence disease risk requires identification of the genes or non-coding RNAs that mediate these associations. Here, we use Capture Hi-C (CHi-C) to annotate 63 loci; we identify 110 putative target genes at 33 loci. To assess the support for these target genes in other data sources we test for associations between levels of expression and SNP genotype (eQTLs), disease-specific survival (DSS), and compare them with somatically mutated cancer genes. 22 putative target genes are eQTLs, 32 are associated with DSS and 14 are somatically mutated in breast, or other, cancers. Identifying the target genes at GWAS risk loci will lead to a greater understanding of the mechanisms that influence breast cancer risk and prognosis.

引用

页数：13

共 54 条

[1] Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2 [J].

Ahmed, Shahana ;

Thomas, Gilles ;

Ghoussaini, Maya ;

Healey, Catherine S. ;

Humphreys, Manjeet K. ;

Platte, Radka ;

Morrison, Jonathan ;

Maranian, Melanie ;

Pooley, Karen A. ;

Luben, Robert ;

Eccles, Diana ;

Evans, D. Gareth ;

Fletcher, Olivia ;

Johnson, Nichola ;

Silva, Isabel dos Santos ;

Peto, Julian ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Jacobs, Kevin ;

Prentice, Ross ;

Anderson, Garnet L. ;

Rajkovic, Aleksandar ;

Curb, J. David ;

Ziegler, Regina G. ;

Berg, Christine D. ;

Buys, Saundra S. ;

McCarty, Catherine A. ;

Feigelson, Heather Spencer ;

Calle, Eugenia E. ;

Thun, Michael J. ;

Diver, W. Ryan ;

Bojesen, Stig ;

Nordestgaard, Borge G. ;

Flyger, Henrik ;

Doerk, Thilo ;

Schuermann, Peter ;

Hillemanns, Peter ;

Karstens, Johann H. ;

Bogdanova, Natalia V. ;

Antonenkova, Natalia N. ;

Zalutsky, Iosif V. ;

Bermisheva, Marina ;

Fedorova, Sardana ;

Khusnutdinova, Elza ;

Kang, Daehee ;

Yoo, Keun-Young ;

Noh, Dong Young ;

Ahn, Sei-Hyun ;

Devilee, Peter ;

van Asperen, Christi J. .

NATURE GENETICS, 2009, 41 (05) :585-590

[2] A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population [J].

Antoniou, Antonis C. ;

Wang, Xianshu ;

Fredericksen, Zachary S. ;

McGuffog, Lesley ;

Tarrell, Robert ;

Sinilnikova, Olga M. ;

Healey, Sue ;

Morrison, Jonathan ;

Kartsonaki, Christiana ;

Lesnick, Timothy ;

Ghoussaini, Maya ;

Barrowdale, Daniel ;

Peock, Susan ;

Cook, Margaret ;

Oliver, Clare ;

Frost, Debra ;

Eccles, Diana ;

Evans, D. Gareth ;

Eeles, Ros ;

Izatt, Louise ;

Chu, Carol ;

Douglas, Fiona ;

Paterson, Joan ;

Stoppa-Lyonnet, Dominique ;

Houdayer, Claude ;

Mazoyer, Sylvie ;

Giraud, Sophie ;

Lasset, Christine ;

Remenieras, Audrey ;

Caron, Olivier ;

Hardouin, Agnes ;

Berthet, Pascaline ;

Hogervorst, Frans B. L. ;

Rookus, Matti A. ;

Jager, Agnes ;

van den Ouweland, Ans ;

Hoogerbrugge, Nicoline ;

van der Luijt, Rob B. ;

Meijers-Heijboer, Hanne ;

Garcia, Encarna B. Gomez ;

Devilee, Peter ;

Vreeswijk, Maaike P. G. ;

Lubinski, Jan ;

Jakubowska, Anna ;

Gronwald, Jacek ;

Huzarski, Tomasz ;

Byrski, Tomasz ;

Gorski, Bohdan ;

Cybulski, Cezary ;

Spurdle, Amanda B. .

NATURE GENETICS, 2010, 42 (10) :885-+

[3] Hi-C: A comprehensive technique to capture the conformation of genomes [J].

Belton, Jon-Matthew ;

McCord, Rachel Patton ;

Gibcus, Johan Harmen ;

Naumova, Natalia ;

Zhan, Ye ;

Dekker, Job .

METHODS, 2012, 58 (03) :268-276

[4] Controlling the false discovery rate in behavior genetics research [J].

Benjamini, Y ;

Drai, D ;

Elmer, G ;

Kafkafi, N ;

Golani, I .

BEHAVIOURAL BRAIN RESEARCH, 2001, 125 (1-2) :279-284

[5] Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer [J].

Bojesen, Stig E. ;

Pooley, Karen A. ;

Johnatty, Sharon E. ;

Beesley, Jonathan ;

Michailidou, Kyriaki ;

Tyrer, Jonathan P. ;

Edwards, Stacey L. ;

Pickett, Hilda A. ;

Shen, Howard C. ;

Smart, Chanel E. ;

Hillman, Kristine M. ;

Mai, Phuong L. ;

Lawrenson, Kate ;

Stutz, Michael D. ;

Lu, Yi ;

Karevan, Rod ;

Woods, Nicholas ;

Johnston, Rebecca L. ;

French, Juliet D. ;

Chen, Xiaoqing ;

Weischer, Maren ;

Nielsen, Sune F. ;

Maranian, Melanie J. ;

Ghoussaini, Maya ;

Ahmed, Shahana ;

Baynes, Caroline ;

Bolla, Manjeet K. ;

Wang, Qin ;

Dennis, Joe ;

McGuffog, Lesley ;

Barrowdale, Daniel ;

Lee, Andrew ;

Healey, Sue ;

Lush, Michael ;

Tessier, Daniel C. ;

Vincent, Daniel ;

Bacot, Francis ;

Vergote, Ignace ;

Lambrechts, Sandrina ;

Despierre, Evelyn ;

Risch, Harvey A. ;

Gonzalez-Neira, Anna ;

Rossing, Mary Anne ;

Pita, Guillermo ;

Doherty, Jennifer A. ;

Alvarez, Nuria ;

Larson, Melissa C. ;

Fridley, Brooke L. ;

Schoof, Nils ;

Chang-Claude, Jenny .

NATURE GENETICS, 2013, 45 (04) :371-384

[6] The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups [J].

Curtis, Christina ;

Shah, Sohrab P. ;

Chin, Suet-Feung ;

Turashvili, Gulisa ;

Rueda, Oscar M. ;

Dunning, Mark J. ;

Speed, Doug ;

Lynch, Andy G. ;

Samarajiwa, Shamith ;

Yuan, Yinyin ;

Graef, Stefan ;

Ha, Gavin ;

Haffari, Gholamreza ;

Bashashati, Ali ;

Russell, Roslin ;

McKinney, Steven ;

Langerod, Anita ;

Green, Andrew ;

Provenzano, Elena ;

Wishart, Gordon ;

Pinder, Sarah ;

Watson, Peter ;

Markowetz, Florian ;

Murphy, Leigh ;

Ellis, Ian ;

Purushotham, Arnie ;

Borresen-Dale, Anne-Lise ;

Brenton, James D. ;

Tavare, Simon ;

Caldas, Carlos ;

Aparicio, Samuel .

NATURE, 2012, 486 (7403) :346-352

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

Darabi, Hatef ;

Beesley, Jonathan ;

Droit, Arnaud ;

Kar, Siddhartha ;

Nord, Silje ;

Marjaneh, Mahdi Moradi ;

Soucy, Penny ;

Michailidou, Kyriaki ;

Ghoussaini, Maya ;

Wahl, Hanna Fues ;

Bolla, Manjeet K. ;

Wang, Qin ;

Dennis, Joe ;

Alonso, M. Rosario ;

Andrulis, Irene L. ;

Anton-Culver, Hoda ;

Arndt, Volker ;

Beckmann, Matthias W. ;

Benitez, Javier ;

Bogdanova, Natalia V. ;

Bojesen, Stig E. ;

Brauch, Hiltrud ;

Brenner, Hermann ;

Broeks, Annegien ;

Bruening, Thomas ;

Burwinkel, Barbara ;

Chang-Claude, Jenny ;

Choi, Ji-Yeob ;

Conroy, Don M. ;

Couch, Fergus J. ;

Cox, Angela ;

Cross, Simon S. ;

Czene, Kamila ;

Devilee, Peter ;

Doerk, Thilo ;

Easton, Douglas F. ;

Fasching, Peter A. ;

Figueroa, Jonine ;

Fletcher, Olivia ;

Flyger, Henrik ;

Galle, Eva ;

Garcia-Closas, Montserrat ;

Giles, Graham G. ;

Goldberg, Mark S. ;

Gonzalez-Neira, Anna ;

Guenel, Pascal ;

Haiman, Christopher A. ;

Hallberg, Emily ;

Hamann, Ute ;

Hartman, Mikael .

SCIENTIFIC REPORTS, 2016, 6

[8] Topology of mammalian developmental enhancers and their regulatory landscapes [J].

de Laat, Wouter ;

Duboule, Denis .

NATURE, 2013, 502 (7472) :499-506

[9] Breast Cancer Statistics, 2013 [J].

DeSantis, Carol ;

Ma, Jiemin ;

Bryan, Leah ;

Jemal, Ahmedin .

CA-A CANCER JOURNAL FOR CLINICIANS, 2014, 64 (01) :52-62

[10] Unbiased analysis of potential targets of breast cancer susceptibility loci by Capture Hi-C [J].

Dryden, Nicola H. ;

Broome, Laura R. ;

Dudbridge, Frank ;

Johnson, Nichola ;

Orr, Nick ;

Schoenfelder, Stefan ;

Nagano, Takashi ;

Andrews, Simon ;

Wingett, Steven ;

Kozarewa, Lwanka ;

Assiotis, Loannis ;

Fenwick, Kerry ;

Maguire, Sarah L. ;

Campbell, James ;

Natrajan, Rachael ;

Lambros, Maryou ;

Perrakis, Eleni ;

Ashworth, Alan ;

Fraser, Peter ;

Fletcher, Olivia .

GENOME RESEARCH, 2014, 24 (11) :1854-1868

← 1 2 3 4 5 6 →