Functional annotation of breast cancer risk loci: current progress and future directions.
Functional annotation of breast cancer risk loci: current progress and future directions.
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DOI：
10.1038/s41416-021-01612-6
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发表时间：
2022-04
影响因子：
8.8
通讯作者：
Fletcher O
中科院分区：
文献类型：
--
作者：
Romualdo Cardoso S;Gillespie A;Haider S;Fletcher O
全基因组关联研究，再加上大规模复制和精细作图研究，已经确定了150多个与乳腺癌风险相关的基因组区域。在这里，我们回顾了将这些发现转化为对疾病机制的更好理解的努力。我们的审查是在最近发表的对这些区域的精细图谱分析的背景下进行的，该分析报告了352个独立信号和总共13,367个可信的因果变异。绝大多数可信的因果变异映射到非编码DNA，暗示基因表达调控是功能变异影响风险的机制。因此，我们回顾了定义候选调控序列的方法，识别假定的靶基因的方法，以及将候选调控序列连接到假定的靶基因的方法。我们提供了可用数据资源的摘要，并找出了这些资源中的差距。我们的结论是，虽然已经做了很多工作，但仍有很多工作要做。然而，也有乐观的理由；将精细绘制的统计数据与使用新技术生成的更能代表正常“风险”乳房的功能数据结合起来，应该会让人们更好地理解影响女性患乳腺癌风险的机制。
Genome-wide association studies coupled with large-scale replication and fine-scale mapping studies have identified more than 150 genomic regions that are associated with breast cancer risk. Here, we review efforts to translate these findings into a greater understanding of disease mechanism. Our review comes in the context of a recently published fine-scale mapping analysis of these regions, which reported 352 independent signals and a total of 13,367 credible causal variants. The vast majority of credible causal variants map to noncoding DNA, implicating regulation of gene expression as the mechanism by which functional variants influence risk. Accordingly, we review methods for defining candidate-regulatory sequences, methods for identifying putative target genes and methods for linking candidate-regulatory sequences to putative target genes. We provide a summary of available data resources and identify gaps in these resources. We conclude that while much work has been done, there is still much to do. There are, however, grounds for optimism; combining statistical data from fine-scale mapping with functional data that are more representative of the normal “at risk” breast, generated using new technologies, should lead to a greater understanding of the mechanisms that influence an individual woman’s 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：
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：
30.8
作者：
Carroll, Jason S.;Meyer, Clifford A.;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
9.8
作者：
Baxter JS;Johnson N;Tomczyk K;Gillespie A;Maguire S;Brough R;Fachal L;Michailidou K;Bolla MK;Wang Q;Dennis J;Ahearn TU;Andrulis IL;Anton-Culver H;Antonenkova NN;Arndt V;Aronson KJ;Augustinsson A;Becher H;Beckmann MW;Behrens S;Benitez J;Bermisheva M;Bogdanova NV;Bojesen SE;Brenner H;Brucker SY;Cai Q;Campa D;Canzian F;Castelao JE;Chan TL;Chang-Claude J;Chanock SJ;Chenevix-Trench G;Choi JY;Clarke CL;NBCS Collaborators;Colonna S;Conroy DM;Couch FJ;Cox A;Cross SS;Czene K;Daly MB;Devilee P;Dörk T;Dossus L;Dwek M;Eccles DM;Ekici AB;Eliassen AH;Engel C;Fasching PA;Figueroa J;Flyger H;Gago-Dominguez M;Gao C;García-Closas M;García-Sáenz JA;Ghoussaini M;Giles GG;Goldberg MS;González-Neira A;Guénel P;Gündert M;Haeberle L;Hahnen E;Haiman CA;Hall P;Hamann U;Hartman M;Hatse S;Hauke J;Hollestelle A;Hoppe R;Hopper JL;Hou MF;kConFab Investigators;ABCTB Investigators;Ito H;Iwasaki M;Jager A;Jakubowska A;Janni W;John EM;Joseph V;Jung A;Kaaks R;Kang D;Keeman R;Khusnutdinova E;Kim SW;Kosma VM;Kraft P;Kristensen VN;Kubelka-Sabit K;Kurian AW;Kwong A;Lacey JV;Lambrechts D;Larson NL;Larsson SC;Le Marchand L;Lejbkowicz F;Li J;Long J;Lophatananon A;Lubiński J;Mannermaa A;Manoochehri M;Manoukian S;Margolin S;Matsuo K;Mavroudis D;Mayes R;Menon U;Milne RL;Mohd Taib NA;Muir K;Muranen TA;Murphy RA;Nevanlinna H;O'Brien KM;Offit K;Olson JE;Olsson H;Park SK;Park-Simon TW;Patel AV;Peterlongo P;Peto J;Plaseska-Karanfilska D;Presneau N;Pylkäs K;Rack B;Rennert G;Romero A;Ruebner M;Rüdiger T;Saloustros E;Sandler DP;Sawyer EJ;Schmidt MK;Schmutzler RK;Schneeweiss A;Schoemaker MJ;Shah M;Shen CY;Shu XO;Simard J;Southey MC;Stone J;Surowy H;Swerdlow AJ;Tamimi RM;Tapper WJ;Taylor JA;Teo SH;Teras LR;Terry MB;Toland AE;Tomlinson I;Truong T;Tseng CC;Untch M;Vachon CM;van den Ouweland AMW;Wang SS;Weinberg CR;Wendt C;Winham SJ;Winqvist R;Wolk A;Wu AH;Yamaji T;Zheng W;Ziogas A;Pharoah PDP;Dunning AM;Easton DF;Pettitt SJ;Lord CJ;Haider S;Orr N;Fletcher O
通讯作者：
Fletcher O
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