Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.
Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.
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DOI：
10.1038/s41467-018-04109-8
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发表时间：
2018-06-11
影响因子：
16.6
通讯作者：
Kote-Jarai Z
中科院分区：
文献类型：
--
作者：
Dadaev T;Saunders EJ;Newcombe PJ;Anokian E;Leongamornlert DA;Brook MN;Cieza-Borrella C;Mijuskovic M;Wakerell S;Olama AAA;Schumacher FR;Berndt SI;Benlloch S;Ahmed M;Goh C;Sheng X;Zhang Z;Muir K;Govindasami K;Lophatananon A;Stevens VL;Gapstur SM;Carter BD;Tangen CM;Goodman P;Thompson IM Jr;Batra J;Chambers S;Moya L;Clements J;Horvath L;Tilley W;Risbridger G;Gronberg H;Aly M;Nordström T;Pharoah P;Pashayan N;Schleutker J;Tammela TLJ;Sipeky C;Auvinen A;Albanes D;Weinstein S;Wolk A;Hakansson N;West C;Dunning AM;Burnet N;Mucci L;Giovannucci E;Andriole G;Cussenot O;Cancel-Tassin G;Koutros S;Freeman LEB;Sorensen KD;Orntoft TF;Borre M;Maehle L;Grindedal EM;Neal DE;Donovan JL;Hamdy FC;Martin RM;Travis RC;Key TJ;Hamilton RJ;Fleshner NE;Finelli A;Ingles SA;Stern MC;Rosenstein B;Kerns S;Ostrer H;Lu YJ;Zhang HW;Feng N;Mao X;Guo X;Wang G;Sun Z;Giles GG;Southey MC;MacInnis RJ;FitzGerald LM;Kibel AS;Drake BF;Vega A;Gómez-Caamaño A;Fachal L;Szulkin R;Eklund M;Kogevinas M;Llorca J;Castaño-Vinyals G;Penney KL;Stampfer M;Park JY;Sellers TA;Lin HY;Stanford JL;Cybulski C;Wokolorczyk D;Lubinski J;Ostrander EA;Geybels MS;Nordestgaard BG;Nielsen SF;Weisher M;Bisbjerg R;Røder MA;Iversen P;Brenner H;Cuk K;Holleczek B;Maier C;Luedeke M;Schnoeller T;Kim J;Logothetis CJ;John EM;Teixeira MR;Paulo P;Cardoso M;Neuhausen SL;Steele L;Ding YC;De Ruyck K;De Meerleer G;Ost P;Razack A;Lim J;Teo SH;Lin DW;Newcomb LF;Lessel D;Gamulin M;Kulis T;Kaneva R;Usmani N;Slavov C;Mitev V;Parliament M;Singhal S;Claessens F;Joniau S;Van den Broeck T;Larkin S;Townsend PA;Aukim-Hastie C;Gago-Dominguez M;Castelao JE;Martinez ME;Roobol MJ;Jenster G;van Schaik RHN;Menegaux F;Truong T;Koudou YA;Xu J;Khaw KT;Cannon-Albright L;Pandha H;Michael A;Kierzek A;Thibodeau SN;McDonnell SK;Schaid DJ;Lindstrom S;Turman C;Ma J;Hunter DJ;Riboli E;Siddiq A;Canzian F;Kolonel LN;Le Marchand L;Hoover RN;Machiela MJ;Kraft P;PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium;Freedman M;Wiklund F;Chanock S;Henderson BE;Easton DF;Haiman CA;Eeles RA;Conti DV;Kote-Jarai Z
前列腺癌是一种具有大量遗传成分的多基因疾病。通过 GWAS 已确定了一些常见的、低外显率的前列腺癌风险位点。在这里，我们使用来自大型欧洲血统荟萃分析的汇总数据，应用贝叶斯多元变量选择算法 JAM 来精细绘制 84 个前列腺癌易感性位点。我们在 12 个地区观察到多个独立信号的证据，总共观察到 99 个风险信号。已确定的候选变异目录中只剩下 15 个原始 GWAS 标签 SNP；其余的人被更有可能的候选人取代。我们可靠的变体集的生物学注释表明启动子和增强子元件以及转录因子结合位点（包括 AR、ERG 和 FOXA1）显着富集。在 40 个区域中，至少一种变异与前列腺癌组织中的 eQTL 共定位。精确的候选变异组大大增加了由这些已知易感区域解释的家族相对风险的比例，这凸显了精细绘图研究的重要性并对临床风险分析具有影响。前列腺癌 (PrCa) 涉及大量可遗传的遗传成分。在这里，作者对已知的 PrCa GWAS 位点进行了多变量精细定位，识别了生物功能丰富的变异，解释了更多的家族相对风险，并在临床风险分析中具有潜在的应用。
Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.
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Snagger：一个用户友好的程序，用于合并用于TAGSNP选择的其他信息。
影响因子：
3
作者：
Edlund, Christopher K.;Lee, Won H.;Li, Dalin;Van Den Berg, David J.;Conti, David V.
通讯作者：
Conti, David V.
DOI：
10.1056/nejmoa1110000
发表时间：
2012-01-12
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ewing CM;Ray AM;Lange EM;Zuhlke KA;Robbins CM;Tembe WD;Wiley KE;Isaacs SD;Johng D;Wang Y;Bizon C;Yan G;Gielzak M;Partin AW;Shanmugam V;Izatt T;Sinari S;Craig DW;Zheng SL;Walsh PC;Montie JE;Xu J;Carpten JD;Isaacs WB;Cooney KA
通讯作者：
Cooney KA
DOI：
10.1093/bioinformatics/btv690
发表时间：
2016-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Dadaev T;Leongamornlert DA;Saunders EJ;Eeles R;Kote-Jarai Z
通讯作者：
Kote-Jarai Z
影响因子：
2.1
作者：
Fridley, Brooke L.
通讯作者：
Fridley, Brooke L.
影响因子：
30.8
作者：
通讯作者：
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