Genetic variants demonstrating flip-flop phenomenon and breast cancer risk prediction among women of African ancestry.
Genetic variants demonstrating flip-flop phenomenon and breast cancer risk prediction among women of African ancestry.
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DOI：
10.1007/s10549-017-4638-1
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发表时间：
2018-04
影响因子：
3.8
通讯作者：
Huo D
中科院分区：
文献类型：
--
作者：
Wang S;Qian F;Zheng Y;Ogundiran T;Ojengbede O;Zheng W;Blot W;Nathanson KL;Hennis A;Nemesure B;Ambs S;Olopade OI;Huo D
很少有研究评估现有的乳腺癌风险预测模型在非洲裔妇女中的表现。在遗传变异的复制研究中，风险关联方向的变化是一种常见现象。术语flip-flop，它意味着一个变异在一个人群中是风险因素，但在另一个人群中是保护性的，影响风险预测模型的性能。我们使用了来自非洲散居者乳腺癌全基因组关联研究（GWAS）（The Root consortium）的数据，该研究包括来自尼日利亚、美国和巴巴多斯的3，686名非洲血统的参与者。多基因风险评分（PRSs）是根据四组乳腺癌易感基因座的优势比（OR）构建的。使用受试者工作特征曲线下面积（AUC）测量辨别能力。在所有研究中，30%~40%的变异体存在翻转现象。使用先前研究中具有一致方向性的34个变体，我们构建了AUC为0.531的PRS（95%置信区间[CI]：0.512-0.550），这与使用93个变体和欧洲血统人群OR的PRS（AUC=0.525，95% CI：0.506-0.544）相似。此外，我们发现34变PRS对有乳腺癌家族史的女性有很好的判别准确性（AUC=0.586，95%CI：0.532-0.640）。总之，我们发现，基于先前在欧洲和亚洲血统女性中进行的GWAS中确定的变异的PRS没有为非洲血统女性提供可比程度的风险分层。在非洲血统人群中进行进一步的大规模精细定位研究，以发现人群特异性遗传风险变异是可取的。
Few studies have evaluated the performance of existing breast cancer risk prediction models among women of African ancestry. In replication studies of genetic variants, a change in direction of the risk association is a common phenomenon. Termed flip-flop, it means that a variant is risk factor in one population but protective in another, affecting the performance of risk prediction models. We used data from the genome-wide association study (GWAS) of breast cancer in the African diaspora (The Root consortium), which included 3,686 participants of African ancestry from Nigeria, USA, and Barbados. Polygenic risk scores (PRSs) were constructed from the published odds ratios (ORs) of four sets of susceptibility loci for breast cancer. Discrimination capacity was measured using the area under the receiver operating characteristic curve (AUC). Flip-flop phenomenon was observed among 30%~40% of variants across studies. Using the 34 variants with consistent directionality among previous studies, we constructed a PRS with AUC of 0.531 (95% confidence interval [CI]: 0.512–0.550), which is similar to the PRS using 93 variants and ORs from European ancestry populations (AUC=0.525, 95% CI: 0.506–0.544). Additionally, we found the 34-variant PRS has good discriminative accuracy in women with family history of breast cancer (AUC=0.586, 95% CI: 0.532–0.640). In conclusion, we found that PRS based on variants identified from prior GWASs conducted in women of European and Asian ancestries did not provide a comparable degree of risk stratification for women of African ancestry. Further large-scale fine-mapping studies in African ancestry populations are desirable to discover population-specific genetic risk variants.
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影响因子：
5.5
作者：
Khoury MJ;Iademarco MF;Riley WT
通讯作者：
Riley WT
影响因子：
30.8
作者：
Michailidou K;Beesley J;Lindstrom S;Canisius S;Dennis J;Lush MJ;Maranian MJ;Bolla MK;Wang Q;Shah M;Perkins BJ;Czene K;Eriksson M;Darabi H;Brand JS;Bojesen SE;Nordestgaard BG;Flyger H;Nielsen SF;Rahman N;Turnbull C;BOCS;Fletcher O;Peto J;Gibson L;dos-Santos-Silva I;Chang-Claude J;Flesch-Janys D;Rudolph A;Eilber U;Behrens S;Nevanlinna H;Muranen TA;Aittomäki K;Blomqvist C;Khan S;Aaltonen K;Ahsan H;Kibriya MG;Whittemore AS;John EM;Malone KE;Gammon MD;Santella RM;Ursin G;Makalic E;Schmidt DF;Casey G;Hunter DJ;Gapstur SM;Gaudet MM;Diver WR;Haiman CA;Schumacher F;Henderson BE;Le Marchand L;Berg CD;Chanock SJ;Figueroa J;Hoover RN;Lambrechts D;Neven P;Wildiers H;van Limbergen E;Schmidt MK;Broeks A;Verhoef S;Cornelissen S;Couch FJ;Olson JE;Hallberg E;Vachon C;Waisfisz Q;Meijers-Heijboer H;Adank MA;van der Luijt RB;Li J;Liu J;Humphreys K;Kang D;Choi JY;Park SK;Yoo KY;Matsuo K;Ito H;Iwata H;Tajima K;Guénel P;Truong T;Mulot C;Sanchez M;Burwinkel B;Marme F;Surowy H;Sohn C;Wu AH;Tseng CC;Van Den Berg D;Stram DO;González-Neira A;Benitez J;Zamora MP;Perez JI;Shu XO;Lu W;Gao YT;Cai H;Cox A;Cross SS;Reed MW;Andrulis IL;Knight JA;Glendon G;Mulligan AM;Sawyer EJ;Tomlinson I;Kerin MJ;Miller N;kConFab Investigators;AOCS Group;Lindblom A;Margolin S;Teo SH;Yip CH;Taib NA;Tan GH;Hooning MJ;Hollestelle A;Martens JW;Collée JM;Blot W;Signorello LB;Cai Q;Hopper JL;Southey MC;Tsimiklis H;Apicella C;Shen CY;Hsiung CN;Wu PE;Hou MF;Kristensen VN;Nord S;Alnaes GI;NBCS;Giles GG;Milne RL;McLean C;Canzian F;Trichopoulos D;Peeters P;Lund E;Sund M;Khaw KT;Gunter MJ;Palli D;Mortensen LM;Dossus L;Huerta JM;Meindl A;Schmutzler RK;Sutter C;Yang R;Muir K;Lophatananon A;Stewart-Brown S;Siriwanarangsan P;Hartman M;Miao H;Chia KS;Chan CW;Fasching PA;Hein A;Beckmann MW;Haeberle L;Brenner H;Dieffenbach AK;Arndt V;Stegmaier C;Ashworth A;Orr N;Schoemaker MJ;Swerdlow AJ;Brinton L;Garcia-Closas M;Zheng W;Halverson SL;Shrubsole M;Long J;Goldberg MS;Labrèche F;Dumont M;Winqvist R;Pylkäs K;Jukkola-Vuorinen A;Grip M;Brauch H;Hamann U;Brüning T;GENICA Network;Radice P;Peterlongo P;Manoukian S;Bernard L;Bogdanova NV;Dörk T;Mannermaa A;Kataja V;Kosma VM;Hartikainen JM;Devilee P;Tollenaar RA;Seynaeve C;Van Asperen CJ;Jakubowska A;Lubinski J;Jaworska K;Huzarski T;Sangrajrang S;Gaborieau V;Brennan P;McKay J;Slager S;Toland AE;Ambrosone CB;Yannoukakos D;Kabisch M;Torres D;Neuhausen SL;Anton-Culver H;Luccarini C;Baynes C;Ahmed S;Healey CS;Tessier DC;Vincent D;Bacot F;Pita G;Alonso MR;Álvarez N;Herrero D;Simard J;Pharoah PP;Kraft P;Dunning AM;Chenevix-Trench G;Hall P;Easton DF
通讯作者：
Easton DF
DOI：
10.1186/s13058-016-0786-1
发表时间：
2016-12-08
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Wen W;Shu XO;Guo X;Cai Q;Long J;Bolla MK;Michailidou K;Dennis J;Wang Q;Gao YT;Zheng Y;Dunning AM;García-Closas M;Brennan P;Chen ST;Choi JY;Hartman M;Ito H;Lophatananon A;Matsuo K;Miao H;Muir K;Sangrajrang S;Shen CY;Teo SH;Tseng CC;Wu AH;Yip CH;Simard J;Pharoah PD;Hall P;Kang D;Xiang Y;Easton DF;Zheng W
通讯作者：
Zheng W
DOI：
10.1038/gim.2014.143
发表时间：
2015-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Kong SW;Lee IH;Leshchiner I;Krier J;Kraft P;Rehm HL;Green RC;Kohane IS;MacRae CA;MedSeq Project
通讯作者：
MedSeq Project
DOI：
10.1038/nrg.2016.27
发表时间：
2016-07
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Chatterjee N;Shi J;García-Closas M
通讯作者：
García-Closas M