Capture Hi-C identifies putative target genes at 33 breast cancer risk loci.
Capture Hi-C identifies putative target genes at 33 breast cancer risk loci.
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DOI：
10.1038/s41467-018-03411-9
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发表时间：
2018-03-12
影响因子：
16.6
通讯作者：
Fletcher O
中科院分区：
文献类型：
--
作者：
Baxter JS;Leavy OC;Dryden NH;Maguire S;Johnson N;Fedele V;Simigdala N;Martin LA;Andrews S;Wingett SW;Assiotis I;Fenwick K;Chauhan R;Rust AG;Orr N;Dudbridge F;Haider S;Fletcher O
全基因组关联研究（GWAS）已经确定了大约100个乳腺癌风险位点。将这些发现转化为对影响疾病风险的机制的更好理解，需要鉴定介导这些关联的基因或非编码RNA。在这里，我们使用捕获Hi-C（CHi-C）注释63个位点，我们确定了110个推定的靶基因在33个位点。为了评估其他数据源对这些靶基因的支持，我们测试了表达水平与SNP基因型（eQTL）、疾病特异性生存率（DSS）之间的关联，并将其与体细胞突变的癌症基因进行比较。22个推定的靶基因是eQTL，32个与DSS相关，14个在乳腺癌或其他癌症中发生体细胞突变。确定GWAS风险位点的靶基因将有助于更好地理解影响乳腺癌风险和预后的机制。全基因组关联研究已经确定了乳腺癌的风险位点。在这里，作者使用Capture Hi-C在33个位点鉴定了110个推定的靶基因，并评估了基因表达、SNP基因型和生存率的相关性，为可能影响乳腺癌预后和风险的机制提供了证据。
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. Risk loci for breast cancer have been identified by genome-wide association studies. Here, the authors use Capture Hi-C to identify 110 putative target genes at 33 loci and assessed associations of gene expression, SNP genotype, and survival, providing evidence of mechanisms that may influence the prognosis and risk of breast cancer.
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影响因子：
30.8
作者：
Dunning AM;Michailidou K;Kuchenbaecker KB;Thompson D;French JD;Beesley J;Healey CS;Kar S;Pooley KA;Lopez-Knowles E;Dicks E;Barrowdale D;Sinnott-Armstrong NA;Sallari RC;Hillman KM;Kaufmann S;Sivakumaran H;Moradi Marjaneh M;Lee JS;Hills M;Jarosz M;Drury S;Canisius S;Bolla MK;Dennis J;Wang Q;Hopper JL;Southey MC;Broeks A;Schmidt MK;Lophatananon A;Muir K;Beckmann MW;Fasching PA;Dos-Santos-Silva I;Peto J;Sawyer EJ;Tomlinson I;Burwinkel B;Marme F;Guénel P;Truong T;Bojesen SE;Flyger H;González-Neira A;Perez JI;Anton-Culver H;Eunjung L;Arndt V;Brenner H;Meindl A;Schmutzler RK;Brauch H;Hamann U;Aittomäki K;Blomqvist C;Ito H;Matsuo K;Bogdanova N;Dörk T;Lindblom A;Margolin S;Kosma VM;Mannermaa A;Tseng CC;Wu AH;Lambrechts D;Wildiers H;Chang-Claude J;Rudolph A;Peterlongo P;Radice P;Olson JE;Giles GG;Milne RL;Haiman CA;Henderson BE;Goldberg MS;Teo SH;Yip CH;Nord S;Borresen-Dale AL;Kristensen V;Long J;Zheng W;Pylkäs K;Winqvist R;Andrulis IL;Knight JA;Devilee P;Seynaeve C;Figueroa J;Sherman ME;Czene K;Darabi H;Hollestelle A;van den Ouweland AM;Humphreys K;Gao YT;Shu XO;Cox A;Cross SS;Blot W;Cai Q;Ghoussaini M;Perkins BJ;Shah M;Choi JY;Kang D;Lee SC;Hartman M;Kabisch M;Torres D;Jakubowska A;Lubinski J;Brennan P;Sangrajrang S;Ambrosone CB;Toland AE;Shen CY;Wu PE;Orr N;Swerdlow A;McGuffog L;Healey S;Lee A;Kapuscinski M;John EM;Terry MB;Daly MB;Goldgar DE;Buys SS;Janavicius R;Tihomirova L;Tung N;Dorfling CM;van Rensburg EJ;Neuhausen SL;Ejlertsen B;Hansen TV;Osorio A;Benitez J;Rando R;Weitzel JN;Bonanni B;Peissel B;Manoukian S;Papi L;Ottini L;Konstantopoulou I;Apostolou P;Garber J;Rashid MU;Frost D;EMBRACE;Izatt L;Ellis S;Godwin AK;Arnold N;Niederacher D;Rhiem K;Bogdanova-Markov N;Sagne C;Stoppa-Lyonnet D;Damiola F;GEMO Study Collaborators;Sinilnikova OM;Mazoyer S;Isaacs C;Claes KB;De Leeneer K;de la Hoya M;Caldes T;Nevanlinna H;Khan S;Mensenkamp AR;HEBON;Hooning MJ;Rookus MA;Kwong A;Olah E;Diez O;Brunet J;Pujana MA;Gronwald J;Huzarski T;Barkardottir RB;Laframboise R;Soucy P;Montagna M;Agata S;Teixeira MR;kConFab Investigators;Park SK;Lindor N;Couch FJ;Tischkowitz M;Foretova L;Vijai J;Offit K;Singer CF;Rappaport C;Phelan CM;Greene MH;Mai PL;Rennert G;Imyanitov EN;Hulick PJ;Phillips KA;Piedmonte M;Mulligan AM;Glendon G;Bojesen A;Thomassen M;Caligo MA;Yoon SY;Friedman E;Laitman Y;Borg A;von Wachenfeldt A;Ehrencrona H;Rantala J;Olopade OI;Ganz PA;Nussbaum RL;Gayther SA;Nathanson KL;Domchek SM;Arun BK;Mitchell G;Karlan BY;Lester J;Maskarinec G;Woolcott C;Scott C;Stone J;Apicella C;Tamimi R;Luben R;Khaw KT;Helland Å;Haakensen V;Dowsett M;Pharoah PD;Simard J;Hall P;García-Closas M;Vachon C;Chenevix-Trench G;Antoniou AC;Easton DF;Edwards SL
通讯作者：
Edwards SL
影响因子：
16.6
作者：
Ghoussaini M;Edwards SL;Michailidou K;Nord S;Cowper-Sal Lari R;Desai K;Kar S;Hillman KM;Kaufmann S;Glubb DM;Beesley J;Dennis J;Bolla MK;Wang Q;Dicks E;Guo Q;Schmidt MK;Shah M;Luben R;Brown J;Czene K;Darabi H;Eriksson M;Klevebring D;Bojesen SE;Nordestgaard BG;Nielsen SF;Flyger H;Lambrechts D;Thienpont B;Neven P;Wildiers H;Broeks A;Van't Veer LJ;Th Rutgers EJ;Couch FJ;Olson JE;Hallberg E;Vachon C;Chang-Claude J;Rudolph A;Seibold P;Flesch-Janys D;Peto J;Dos-Santos-Silva I;Gibson L;Nevanlinna H;Muranen TA;Aittomäki K;Blomqvist C;Hall P;Li J;Liu J;Humphreys K;Kang D;Choi JY;Park SK;Noh DY;Matsuo K;Ito H;Iwata H;Yatabe Y;Guénel P;Truong T;Menegaux F;Sanchez M;Burwinkel B;Marme F;Schneeweiss A;Sohn C;Wu AH;Tseng CC;Van Den Berg D;Stram DO;Benitez J;Zamora MP;Perez JI;Menéndez P;Shu XO;Lu W;Gao YT;Cai Q;Cox A;Cross SS;Reed MW;Andrulis IL;Knight JA;Glendon G;Tchatchou S;Sawyer EJ;Tomlinson I;Kerin MJ;Miller N;Haiman CA;Henderson BE;Schumacher F;Le Marchand L;Lindblom A;Margolin S;Teo SH;Yip CH;Lee DS;Wong TY;Hooning MJ;Martens JW;Collée JM;van Deurzen CH;Hopper JL;Southey MC;Tsimiklis H;Kapuscinski MK;Shen CY;Wu PE;Yu JC;Chen ST;Alnæs GG;Borresen-Dale AL;Giles GG;Milne RL;McLean C;Muir K;Lophatananon A;Stewart-Brown S;Siriwanarangsan P;Hartman M;Miao H;Buhari SA;Teo YY;Fasching PA;Haeberle L;Ekici AB;Beckmann MW;Brenner H;Dieffenbach AK;Arndt V;Stegmaier C;Swerdlow A;Ashworth A;Orr N;Schoemaker MJ;García-Closas M;Figueroa J;Chanock SJ;Lissowska J;Simard J;Goldberg MS;Labrèche F;Dumont M;Winqvist R;Pylkäs K;Jukkola-Vuorinen A;Brauch H;Brüning T;Koto YD;Radice P;Peterlongo P;Bonanni B;Volorio S;Dörk T;Bogdanova NV;Helbig S;Mannermaa A;Kataja V;Kosma VM;Hartikainen JM;Devilee P;Tollenaar RA;Seynaeve C;Van Asperen CJ;Jakubowska A;Lubinski J;Jaworska-Bieniek K;Durda K;Slager S;Toland AE;Ambrosone CB;Yannoukakos D;Sangrajrang S;Gaborieau V;Brennan P;McKay J;Hamann U;Torres D;Zheng W;Long J;Anton-Culver H;Neuhausen SL;Luccarini C;Baynes C;Ahmed S;Maranian M;Healey CS;González-Neira A;Pita G;Alonso MR;Alvarez N;Herrero D;Tessier DC;Vincent D;Bacot F;de Santiago I;Carroll J;Caldas C;Brown MA;Lupien M;Kristensen VN;Pharoah PD;Chenevix-Trench G;French JD;Easton DF;Dunning AM;Australian Ovarian Cancer Management Group;Australian Ovarian Cancer Management Group
通讯作者：
Australian Ovarian Cancer Management Group
影响因子：
7
作者：
Dryden NH;Broome LR;Dudbridge F;Johnson N;Orr N;Schoenfelder S;Nagano T;Andrews S;Wingett S;Kozarewa I;Assiotis I;Fenwick K;Maguire SL;Campbell J;Natrajan R;Lambros M;Perrakis E;Ashworth A;Fraser P;Fletcher O
通讯作者：
Fletcher O
影响因子：
254.7
作者：
DeSantis, Carol;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
64.8
作者：
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
通讯作者：
Aparicio, Samuel