Department of Medicine, Section of Epidemiology and Population Sciences, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
Institute for Clinical and Translational Research, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
Neuro Oncol. 2021 Aug 2;23(8):1304-1314. doi: 10.1093/neuonc/noab072.
Epidemiological studies of adult glioma have identified genetic syndromes and 25 heritable risk loci that modify individual risk for glioma, as well increased risk in association with exposure to ionizing radiation and decreased risk in association with allergies. In this analysis, we assess whether there is a shared genome-wide genetic architecture between glioma and atopic/autoimmune diseases.
Using summary statistics from a glioma genome-wide association studies (GWAS) meta-analysis, we identified significant enrichment for risk variants associated with gene expression changes in immune cell populations. We also estimated genetic correlations between glioma and autoimmune, atopic, and hematologic traits using linkage disequilibrium score regression (LDSC), which leverages genome-wide single-nucleotide polymorphism (SNP) associations and patterns of linkage disequilibrium.
Nominally significant negative correlations were observed for glioblastoma (GB) and primary biliary cirrhosis (rg = -0.26, P = .0228), and for non-GB gliomas and celiac disease (rg = -0.32, P = .0109). Our analyses implicate dendritic cells (GB pHM = 0.0306 and non-GB pHM = 0.0186) in mediating both GB and non-GB genetic predisposition, with GB-specific associations identified in natural killer (NK) cells (pHM = 0.0201) and stem cells (pHM = 0.0265).
This analysis identifies putative new associations between glioma and autoimmune conditions with genomic architecture that is inversely correlated with that of glioma and that T cells, NK cells, and myeloid cells are involved in mediating glioma predisposition. This provides further evidence that increased activation of the acquired immune system may modify individual susceptibility to glioma.
成人脑胶质瘤的流行病学研究已经确定了一些遗传综合征和 25 个遗传性风险位点，这些风险因素可以改变个体患脑胶质瘤的风险，同时与电离辐射暴露相关的风险增加，与过敏相关的风险降低。在这项分析中，我们评估了脑胶质瘤和特应性/自身免疫性疾病之间是否存在全基因组遗传结构共享。
使用脑胶质瘤全基因组关联研究（GWAS）荟萃分析的汇总统计数据，我们确定了与免疫细胞群体基因表达变化相关的风险变异体的显著富集。我们还使用基于连锁不平衡得分回归（LDSC）的方法估计了脑胶质瘤与自身免疫、特应性和血液学特征之间的遗传相关性，该方法利用全基因组单核苷酸多态性（SNP）关联和连锁不平衡模式。
我们观察到胶质母细胞瘤（GB）和原发性胆汁性肝硬化（rg = -0.26，P =.0228）之间以及非 GB 胶质瘤和乳糜泻（rg = -0.32，P =.0109）之间存在名义上显著的负相关。我们的分析表明树突状细胞（GB pHM = 0.0306 和非 GB pHM = 0.0186）介导了 GB 和非 GB 的遗传易感性，在自然杀伤（NK）细胞（pHM = 0.0201）和干细胞（pHM = 0.0265）中发现了特定于 GB 的关联。
这项分析确定了脑胶质瘤与自身免疫性疾病之间的潜在新关联，其基因组结构与脑胶质瘤的基因组结构相反，并且 T 细胞、NK 细胞和髓样细胞参与介导脑胶质瘤易感性。这进一步证明了获得性免疫系统的过度激活可能会改变个体患脑胶质瘤的易感性。
