Association analysis identifies 65 new breast cancer risk loci.
Association analysis identifies 65 new breast cancer risk loci.
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DOI：
10.1038/nature24284
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发表时间：
2017-11-02
期刊：
影响因子：
64.8
通讯作者：
Easton DF
中科院分区：
文献类型：
--
作者：
Michailidou K;Lindström S;Dennis J;Beesley J;Hui S;Kar S;Lemaçon A;Soucy P;Glubb D;Rostamianfar A;Bolla MK;Wang Q;Tyrer J;Dicks E;Lee A;Wang Z;Allen J;Keeman R;Eilber U;French JD;Qing Chen X;Fachal L;McCue K;McCart Reed AE;Ghoussaini M;Carroll JS;Jiang X;Finucane H;Adams M;Adank MA;Ahsan H;Aittomäki K;Anton-Culver H;Antonenkova NN;Arndt V;Aronson KJ;Arun B;Auer PL;Bacot F;Barrdahl M;Baynes C;Beckmann MW;Behrens S;Benitez J;Bermisheva M;Bernstein L;Blomqvist C;Bogdanova NV;Bojesen SE;Bonanni B;Børresen-Dale AL;Brand JS;Brauch H;Brennan P;Brenner H;Brinton L;Broberg P;Brock IW;Broeks A;Brooks-Wilson A;Brucker SY;Brüning T;Burwinkel B;Butterbach K;Cai Q;Cai H;Caldés T;Canzian F;Carracedo A;Carter BD;Castelao JE;Chan TL;David Cheng TY;Seng Chia K;Choi JY;Christiansen H;Clarke CL;NBCS Collaborators;Collée M;Conroy DM;Cordina-Duverger E;Cornelissen S;Cox DG;Cox A;Cross SS;Cunningham JM;Czene K;Daly MB;Devilee P;Doheny KF;Dörk T;Dos-Santos-Silva I;Dumont M;Durcan L;Dwek M;Eccles DM;Ekici AB;Eliassen AH;Ellberg C;Elvira M;Engel C;Eriksson M;Fasching PA;Figueroa J;Flesch-Janys D;Fletcher O;Flyger H;Fritschi L;Gaborieau V;Gabrielson M;Gago-Dominguez M;Gao YT;Gapstur SM;García-Sáenz JA;Gaudet MM;Georgoulias V;Giles GG;Glendon G;Goldberg MS;Goldgar DE;González-Neira A;Grenaker Alnæs GI;Grip M;Gronwald J;Grundy A;Guénel P;Haeberle L;Hahnen E;Haiman CA;Håkansson N;Hamann U;Hamel N;Hankinson S;Harrington P;Hart SN;Hartikainen JM;Hartman M;Hein A;Heyworth J;Hicks B;Hillemanns P;Ho DN;Hollestelle A;Hooning MJ;Hoover RN;Hopper JL;Hou MF;Hsiung CN;Huang G;Humphreys K;Ishiguro J;Ito H;Iwasaki M;Iwata H;Jakubowska A;Janni W;John EM;Johnson N;Jones K;Jones M;Jukkola-Vuorinen A;Kaaks R;Kabisch M;Kaczmarek K;Kang D;Kasuga Y;Kerin MJ;Khan S;Khusnutdinova E;Kiiski JI;Kim SW;Knight JA;Kosma VM;Kristensen VN;Krüger U;Kwong A;Lambrechts D;Le Marchand L;Lee E;Lee MH;Lee JW;Neng Lee C;Lejbkowicz F;Li J;Lilyquist J;Lindblom A;Lissowska J;Lo WY;Loibl S;Long J;Lophatananon A;Lubinski J;Luccarini C;Lux MP;Ma ESK;MacInnis RJ;Maishman T;Makalic E;Malone KE;Kostovska IM;Mannermaa A;Manoukian S;Manson JE;Margolin S;Mariapun S;Martinez ME;Matsuo K;Mavroudis D;McKay J;McLean C;Meijers-Heijboer H;Meindl A;Menéndez P;Menon U;Meyer J;Miao H;Miller N;Taib NAM;Muir K;Mulligan AM;Mulot C;Neuhausen SL;Nevanlinna H;Neven P;Nielsen SF;Noh DY;Nordestgaard BG;Norman A;Olopade OI;Olson JE;Olsson H;Olswold C;Orr N;Pankratz VS;Park SK;Park-Simon TW;Lloyd R;Perez JIA;Peterlongo P;Peto J;Phillips KA;Pinchev M;Plaseska-Karanfilska D;Prentice R;Presneau N;Prokofyeva D;Pugh E;Pylkäs K;Rack B;Radice P;Rahman N;Rennert G;Rennert HS;Rhenius V;Romero A;Romm J;Ruddy KJ;Rüdiger T;Rudolph A;Ruebner M;Rutgers EJT;Saloustros E;Sandler DP;Sangrajrang S;Sawyer EJ;Schmidt DF;Schmutzler RK;Schneeweiss A;Schoemaker MJ;Schumacher F;Schürmann P;Scott RJ;Scott C;Seal S;Seynaeve C;Shah M;Sharma P;Shen CY;Sheng G;Sherman ME;Shrubsole MJ;Shu XO;Smeets A;Sohn C;Southey MC;Spinelli JJ;Stegmaier C;Stewart-Brown S;Stone J;Stram DO;Surowy H;Swerdlow A;Tamimi R;Taylor JA;Tengström M;Teo SH;Beth Terry M;Tessier DC;Thanasitthichai S;Thöne K;Tollenaar RAEM;Tomlinson I;Tong L;Torres D;Truong T;Tseng CC;Tsugane S;Ulmer HU;Ursin G;Untch M;Vachon C;van Asperen CJ;Van Den Berg D;van den Ouweland AMW;van der Kolk L;van der Luijt RB;Vincent D;Vollenweider J;Waisfisz Q;Wang-Gohrke S;Weinberg CR;Wendt C;Whittemore AS;Wildiers H;Willett W;Winqvist R;Wolk A;Wu AH;Xia L;Yamaji T;Yang XR;Har Yip C;Yoo KY;Yu JC;Zheng W;Zheng Y;Zhu B;Ziogas A;Ziv E;ABCTB Investigators;ConFab/AOCS Investigators;Lakhani SR;Antoniou AC;Droit A;Andrulis IL;Amos CI;Couch FJ;Pharoah PDP;Chang-Claude J;Hall P;Hunter DJ;Milne RL;García-Closas M;Schmidt MK;Chanock SJ;Dunning AM;Edwards SL;Bader GD;Chenevix-Trench G;Simard J;Kraft P;Easton DF
乳腺癌的风险受到易感基因中罕见的编码变异的影响，如BRCA 1和许多常见的，主要是非编码变异。然而，大部分基因对乳腺癌风险的贡献仍然未知。我们报告了一项乳腺癌全基因组关联研究（GWAS）的结果，该研究包括122，977例欧洲血统的病例和105，974例对照，以及14，068例东亚血统的病例和13，104例对照。我们确定了65个与总体乳腺癌相关的新基因座，p<5x 10 -8。新基因座中的大多数可信风险SNP都位于远端调节元件中，并且通过整合计算机模拟数据来预测每个基因座乳腺细胞中的靶基因，我们证明了乳腺肿瘤中候选靶基因和体细胞驱动基因之间存在很强的重叠。我们还发现，乳腺癌的遗传性，由于所有SNPs的监管功能是2-5倍富集相对于全基因组的平均值，与特定的转录因子结合位点的强烈富集。这些结果为乳腺癌的遗传易感性提供了进一步的见解，并将提高遗传风险评分用于个体化筛查和预防的实用性。
Breast cancer risk is influenced by rare coding variants in susceptibility genes such as BRCA1 and many common, mainly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. We report results from a genome-wide association study (GWAS) of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci associated with overall breast cancer at p<5x10-8. The majority of credible risk SNPs in the new loci fall in distal regulatory elements, and by integrating in-silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all SNPs in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the utility of genetic risk scores for individualized screening and prevention.
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影响因子：
12.3
作者：
Kandasamy K;Mohan SS;Raju R;Keerthikumar S;Kumar GS;Venugopal AK;Telikicherla D;Navarro JD;Mathivanan S;Pecquet C;Gollapudi SK;Tattikota SG;Mohan S;Padhukasahasram H;Subbannayya Y;Goel R;Jacob HK;Zhong J;Sekhar R;Nanjappa V;Balakrishnan L;Subbaiah R;Ramachandra YL;Rahiman BA;Prasad TS;Lin JX;Houtman JC;Desiderio S;Renauld JC;Constantinescu SN;Ohara O;Hirano T;Kubo M;Singh S;Khatri P;Draghici S;Bader GD;Sander C;Leonard WJ;Pandey A
通讯作者：
Pandey A
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
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：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA