Region-Based Analyses of Existing Genome-Wide Association Studies Identifies Novel Potential Genetic Susceptibility Regions for Glioma.

IF 2 Q3 ONCOLOGY Cancer research communications Pub Date : 2024-11-01 DOI:10.1158/2767-9764.CRC-24-0385
Karen Alpen, Robert J Maclnnis, Claire M Vajdic, John Lai, James G Dowty, Eng-Siew Koh, Elizabeth Hovey, Rosemary Harrup, Tuong L Nguyen, Shuai Li, David Joseph, Geza Benke, Pierre-Antoine Dugué, Melissa C Southey, Graham G Giles, Anna K Nowak, Katharine J Drummond, Daniel F Schmidt, John L Hopper, Miroslaw K Kapuscinski, Enes Makalic
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Abstract

Significance: Further investigation of the potential susceptibility regions identified in our study may lead to a better understanding of glioma genetic risk and the underlying biological etiology of glioma. Our study suggests sex may play a role in genetic susceptibility and highlights the importance of sex-specific analysis in future glioma research.

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对现有全基因组关联研究进行基于区域的分析,发现了胶质瘤的新潜在遗传易感区域。
目的:胶质瘤是一种罕见的、使人衰弱的脑癌,是存活率最低的癌症之一。全基因组关联研究发现了 34 个遗传易感区。我们试图利用同时测试连续遗传标记群的方法来发现新的易感区域:我们使用机器学习算法 DEPTH 和基于广义伯克-琼斯(GBJ)统计量的区域回归法分析了三项独立的欧洲血统胶质瘤研究的数据:GliomaScan(1,316 例/1,293 例对照)、AGOG(560 例/2,237 例对照)和 GICC(4,000 例/2,411 例对照),按胶质瘤类型和性别评估了胶质瘤与基因组区域的关联。加州大学旧金山分校/Mayo Clinic 研究的汇总统计用于独立验证。我们利用 GliomaScan、AGOG、GICC 和 UCSF/Mayo 进行了荟萃分析:我们在多项研究中发现了 11 个常见的胶质瘤风险候选基因组区域。根据荟萃分析的结果,这11个区域中有两个分别与女性和男性患胶质瘤的风险显著相关,这两个区域分别是含有RBFOX1的16p13.3和含有PRDM2的1p36.21。这两个区域以前都与胶质瘤肿瘤进展有关。这11个区域中有3个包含神经递质受体基因(7q31.33 GRM8、5q35.2 DRD1、15q13.3 CHRNA7):我们基于区域的方法发现了11个与胶质瘤风险相关的基因组区域,其中16p13.3和1p36.21这两个区域值得进一步研究,它们分别是女性和男性胶质瘤风险的遗传易感区域。我们的分析表明,胶质瘤的遗传易感性可能因性别而异,并强调了突触相关基因在胶质瘤易感性中发挥作用的可能性。
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