Combinations of newly confirmed Glioma-Associated loci link regions on chromosomes 1 and 9 to increased disease risk.
Combinations of newly confirmed Glioma-Associated loci link regions on chromosomes 1 and 9 to increased disease risk.
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新确认的胶质瘤1和9染色体上胶质瘤相关的基因座连接区域的组合，以增加疾病风险。
DOI：
10.1186/1755-8794-4-63
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发表时间：
2011-08-09
影响因子：
2.7
通讯作者：
Delisi C
中科院分区：
文献类型：
--
作者：
Yang TH;Kon M;Hung JH;Delisi C
多形性胶质母细胞瘤 (GBM) 往往发生在 45 岁至 70 岁之间。这种相对较早的发病及其较差的预后使得 GBM 对公共健康的影响远远大于其相对较低的发病率所暗示的影响。现在已经收集了许多人群的组织和血液样本，并通过几项不同的全基因组关联（GWA）研究寻找易感等位基因。 NIH 的癌症基因组图谱 (TCGA) 也收集了大量数据。由于使用不同群体获得的结果之间的一致性较低，因此在两项或多项研究中仅重复了五个基因组区域中的 14 个易感单核苷酸多态性 (SNP) 候选者。本文的目的是提出一种改进的生物标志物识别方法。基于加性遗传模型，在“GBM 和对照 SNP 基因型之间没有关联”的零假设下，使用 EIGENSTRAT 软件包对群体分层进行关联分析。通过连锁不平衡 (LD) 或表达数量性状位点 (eQTL) 分析确定与已识别的 SNP 密切相关的基因。一种结合荟萃分析和通路富集分析的新方法确定了其他基因。 (i) 对 TCGA 和成人胶质瘤研究的 SNP 数据进行荟萃分析，确定了 12 种易感 SNP 候选者，其中 7 种是首次报告。这些 SNP 位于五个基因组区域（5p15.33、9p21.3、1p21.2、3q26.2 和 7p15.3），其中三个区域以前未曾报道过。 (ii) 25 个基因与这 12 个 SNP 密切相关，其中 8 个已知与癌症相关。 (iii) 1 号和 9 号染色体上的风险等位基因组合的 GBM 相对风险最高。 (iv) 综合荟萃分析/通路分析确定了另外四个基因。所有这些都已被确定与癌症相关，但之前并未与神经胶质瘤相关。 (v) 一些在群体中不能重复出现的 SNP 处于可重复（不变）的途径中，这表明它们影响相同的生物过程，并且群体不一致可以通过评估过程而不是基因来部分解决。我们发现了 29 个与神经胶质瘤相关的候选基因；其中 12 种已知与癌症相关 (p = 1. 4 × 10-6)，为新候选者的相关性提供了额外的统计支持。有关风险位点的附加信息对于识别有神经胶质瘤风险的白种人以及评估相对风险可能很重要。
Glioblastoma multiforme (GBM) tends to occur between the ages of 45 and 70. This relatively early onset and its poor prognosis make the impact of GBM on public health far greater than would be suggested by its relatively low frequency. Tissue and blood samples have now been collected for a number of populations, and predisposing alleles have been sought by several different genome-wide association (GWA) studies. The Cancer Genome Atlas (TCGA) at NIH has also collected a considerable amount of data. Because of the low concordance between the results obtained using different populations, only 14 predisposing single nucleotide polymorphism (SNP) candidates in five genomic regions have been replicated in two or more studies. The purpose of this paper is to present an improved approach to biomarker identification. Association analysis was performed with control of population stratifications using the EIGENSTRAT package, under the null hypothesis of "no association between GBM and control SNP genotypes," based on an additive inheritance model. Genes that are strongly correlated with identified SNPs were determined by linkage disequilibrium (LD) or expression quantitative trait locus (eQTL) analysis. A new approach that combines meta-analysis and pathway enrichment analysis identified additional genes. (i) A meta-analysis of SNP data from TCGA and the Adult Glioma Study identifies 12 predisposing SNP candidates, seven of which are reported for the first time. These SNPs fall in five genomic regions (5p15.33, 9p21.3, 1p21.2, 3q26.2 and 7p15.3), three of which have not been previously reported. (ii) 25 genes are strongly correlated with these 12 SNPs, eight of which are known to be cancer-associated. (iii) The relative risk for GBM is highest for risk allele combinations on chromosomes 1 and 9. (iv) A combined meta-analysis/pathway analysis identified an additional four genes. All of these have been identified as cancer-related, but have not been previously associated with glioma. (v) Some SNPs that do not occur reproducibly across populations are in reproducible (invariant) pathways, suggesting that they affect the same biological process, and that population discordance can be partially resolved by evaluating processes rather than genes. We have uncovered 29 glioma-associated gene candidates; 12 of them known to be cancer related (p = 1. 4 × 10-6), providing additional statistical support for the relevance of the new candidates. This additional information on risk loci is potentially important for identifying Caucasian individuals at risk for glioma, and for assessing relative risk.
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影响因子：
12.3
作者：
Hung JH;Whitfield TW;Yang TH;Hu Z;Weng Z;DeLisi C
通讯作者：
DeLisi C
影响因子：
30.8
作者：
Shete S;Hosking FJ;Robertson LB;Dobbins SE;Sanson M;Malmer B;Simon M;Marie Y;Boisselier B;Delattre JY;Hoang-Xuan K;El Hallani S;Idbaih A;Zelenika D;Andersson U;Henriksson R;Bergenheim AT;Feychting M;Lönn S;Ahlbom A;Schramm J;Linnebank M;Hemminki K;Kumar R;Hepworth SJ;Price A;Armstrong G;Liu Y;Gu X;Yu R;Lau C;Schoemaker M;Muir K;Swerdlow A;Lathrop M;Bondy M;Houlston RS
通讯作者：
Houlston RS
影响因子：
30.8
作者：
Skol, AD;Scott, LJ;Boehnke, M
通讯作者：
Boehnke, M
影响因子：
64.8
作者：
Chin, L.;Meyerson, M.;Aldape, K.;Bigner, D.;Mikkelsen, T.;VandenBerg, S.;Kahn, A.;Penny, R.;Ferguson, M. L.;Gerhard, D. S.;Getz, G.;Brennan, C.;Taylor, B. S.;Winckler, W.;Park, P.;Ladanyi, M.;Hoadley, K. A.;Verhaak, R. G. W.;Hayes, D. N.;Spellman, Paul T.;Absher, D.;Weir, B. A.;Ding, L.;Wheeler, D.;Lawrence, M. S.;Cibulskis, K.;Mardis, E.;Zhang, Jinghui;Wilson, R. K.;Donehower, L.;Wheeler, D. A.;Purdom, E.;Wallis, J.;Laird, P. W.;Herman, J. G.;Schuebel, K. E.;Weisenberger, D. J.;Baylin, S. B.;Schultz, N.;Yao, Jun;Wiedemeyer, R.;Weinstein, J.;Sander, C.;Gibbs, R. A.;Gray, J.;Kucherlapati, R.;Lander, E. S.;Myers, R. M.;Perou, C. M.;McLendon, Roger;Friedman, Allan;Van Meir, Erwin G;Brat, Daniel J;Mastrogianakis, Gena Marie;Olson, Jeffrey J;Lehman, Norman;Yung, W. K. Alfred;Bogler, Oliver;Berger, Mitchel;Prados, Michael;Muzny, Donna;Morgan, Margaret;Scherer, Steve;Sabo, Aniko;Nazareth, Lynn;Lewis, Lora;Hall, Otis;Zhu, Yiming;Ren, Yanru;Alvi, Omar;Yao, Jiqiang;Hawes, Alicia;Jhangiani, Shalini;Fowler, Gerald;San Lucas, Anthony;Kovar, Christie;Cree, Andrew;Dinh, Huyen;Santibanez, Jireh;Joshi, Vandita;Gonzalez-Garay, Manuel L.;Miller, Christopher A.;Milosavljevic, Aleksandar;Sougnez, Carrie;Fennell, Tim;Mahan, Scott;Wilkinson, Jane;Ziaugra, Liuda;Onofrio, Robert;Bloom, Toby;Nicol, Rob;Ardlie, Kristin;Baldwin, Jennifer;Gabriel, Stacey;Fulton, Robert S.;McLellan, Michael D.;Larson, David E.;Shi, Xiaoqi;Abbott, Rachel;Fulton, Lucinda;Chen, Ken;Koboldt, Daniel C.;Wendl, Michael C.;Meyer, Rick;Tang, Yuzhu;Lin, Ling;Osborne, John R.;Dunford-Shore, Brian H.;Miner, Tracie L.;Delehaunty, Kim;Markovic, Chris;Swift, Gary;Courtney, William;Pohl, Craig;Abbott, Scott;Hawkins, Amy;Leong, Shin;Haipek, Carrie;Schmidt, Heather;Wiechert, Maddy;Vickery, Tammi;Scott, Sacha;Dooling, David J.;Chinwalla, Asif;Weinstock, George M.;O'Kelly, Michael;Robinson, Jim;Alexe, Gabriele;Beroukhim, Rameen;Carter, Scott;Chiang, Derek;Gould, Josh;Gupta, Supriya;Korn, Josh;Mermel, Craig;Mesirov, Jill;Monti, Stefano;Nguyen, Huy;Parkin, Melissa;Reich, Michael;Stransky, Nicolas;Garraway, Levi;Golub, Todd;Protopopov, Alexei;Perna, Ilana;Aronson, Sandy;Sathiamoorthy, Narayan;Ren, Georgia;Kim, Hyunsoo;Kong, Sek Won;Xiao, Yonghong;Kohane, Isaac S.;Seidman, Jon;Cope, Leslie;Pan, Fei;Van Den Berg, David;Van Neste, Leander;Yi, Joo Mi;Li, Jun Z.;Southwick, Audrey;Brady, Shannon;Aggarwal, Amita;Chung, Tisha;Sherlock, Gavin;Brooks, James D.;Jakkula, Lakshmi R.;Lapuk, Anna V.;Marr, Henry;Dorton, Shannon;Choi, Yoon Gi;Han, Ju;Ray, Amrita;Wang, Victoria;Durinck, Steffen;Robinson, Mark;Wang, Nicholas J.;Vranizan, Karen;Peng, Vivian;Van Name, Eric;Fontenay, Gerald V.;Ngai, John;Conboy, John G.;Parvin, Bahram;Feiler, Heidi S.;Speed, Terence P.;Socci, Nicholas D.;Olshen, Adam;Lash, Alex;Reva, Boris;Antipin, Yevgeniy;Stukalov, Alexey;Gross, Benjamin;Cerami, Ethan;Wang, Wei Qing;Qin, Li-Xuan;Seshan, Venkatraman E.;Villafania, Liliana;Cavatore, Magali;Borsu, Laetitia;Viale, Agnes;Gerald, William;Topal, Michael D.;Qi, Yuan;Balu, Sai;Shi, Yan;Wu, George;Bittner, Michael;Shelton, Troy;Lenkiewicz, Elizabeth;Morris, Scott;Beasley, Debbie;Sanders, Sheri;Sfeir, Robert;Chen, Jessica;Nassau, David;Feng, Larry;Hickey, Erin;Schaefer, Carl;Madhavan, Subha;Buetow, Ken;Barker, Anna;Vockley, Joseph;Compton, Carolyn;Vaught, Jim;Fielding, Peter;Collins, Francis;Good, Peter;Guyer, Mark;Ozenberger, Brad;Peterson, Jane;Thomson, Elizabeth
通讯作者：
Thomson, Elizabeth
影响因子：
30.8
作者：
Stacey, Simon N.;Sulem, Patrick;Masson, Gisli;Gudjonsson, Sigurjon A.;Thorleifsson, Gudmar;Jakobsdottir, Margret;Sigurdsson, Asgeir;Gudbjartsson, Daniel F.;Sigurgeirsson, Bardur;Benediktsdottir, Kristrun R.;Thorisdottir, Kristin;Ragnarsson, Rafn;Scherer, Dominique;Hemminki, Kari;Rudnai, Peter;Gurzau, Eugene;Koppova, Kvetoslava;Botella-Estrada, Rafael;Soriano, Virtudes;Juberias, Pablo;Saez, Berta;Gilaberte, Yolanda;Fuentelsaz, Victoria;Corredera, Cristina;Grasa, Matilde;Hoiom, Veronica;Lindblom, Annika;Bonenkamp, Johannes J.;van Rossum, Michelle M.;Aben, Katja K. H.;de Vries, Esther;Santinami, Mario;Di Mauro, Maria G.;Maurichi, Andrea;Wendt, Judith;Hochleitner, Pia;Pehamberger, Hubert;Gudmundsson, Julius;Magnusdottir, Droplaug N.;Gretarsdottir, Solveig;Holm, Hilma;Steinthorsdottir, Valgerdur;Frigge, Michael L.;Blondal, Thorarinn;Saemundsdottir, Jona;Bjarnason, Hjordis;Kristjansson, Kristleifur;Bjornsdottir, Gyda;Okamoto, Ichiro;Rivoltini, Licia;Rodolfo, Monica;Kiemeney, Lambertus A.;Hansson, Johan;Nagore, Eduardo;Mayordomo, Jose I.;Kumar, Rajiv;Karagas, Margaret R.;Nelson, Heather H.;Gulcher, Jeffrey R.;Rafnar, Thorunn;Thorsteinsdottir, Unnur;Olafsson, Jon H.;Kong, Augustine;Stefansson, Kari
通讯作者：
Stefansson, Kari