European genetic ancestry associated with risk of childhood ependymoma.
European genetic ancestry associated with risk of childhood ependymoma.
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欧洲遗传血统与儿童室管膜瘤的风险相关。
DOI：
10.1093/neuonc/noaa130
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发表时间：
2020
期刊：
影响因子：
15.9
通讯作者：
Barnholtz-Sloan,Jill
中科院分区：
文献类型：
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作者：
Zhang,Chenan;Ostrom,QuinnT;Hansen,HelenM;Gonzalez-Maya,Julio;Hu,Donglei;Ziv,Elad;Morimoto,Libby;deSmith,AdamJ;Muskens,IvoS;Kline,CassieN;Vaksman,Zalman;Hakonarson,Hakon;Diskin,SharonJ;Kruchko,Carol;Barnholtz-Sloan,Jill
依赖性瘤是一种组织学上明确的中枢神经系统肿瘤，最常见于儿童期。观察到不同种族/民族的人群水平发病率差异，欧洲血统的个体风险最高。我们的目的是确定欧洲遗传祖先的程度是否与美国人群的室管膜瘤风险相关。方法在一项针对加利福尼亚儿童的多种族研究中（327例，对照1970例），我们使用全基因组数据估计了最近混合的西班牙裔和非洲裔美国人受试者中欧洲、非洲和美洲原住民血统的比例，并估计了非西班牙裔白人受试者中的欧洲血统。我们测试了全基因组的祖先差异是否与室管膜瘤风险相关，并进行了混合定位以确定与当地祖先的关联。我们还评估了美国中央脑肿瘤登记处（CBTRUS）中按种族/民族分层的室管膜瘤发病率数据。结果sctrus数据显示，与非西班牙裔白人相比，非裔美国人和印第安人儿童的室管膜瘤发病率分别降低了33%和36%。在遗传分析中，在自报的西班牙裔和非裔美国人中，欧洲血统增加20%，室管膜瘤的发病率增加1.31倍（95% CI: 1.08-1.59,Pmeta= 6.7 × 10−3）。此外，东欧祖先亚结构与非西班牙裔白人（P= 0.030）和西班牙裔白人（P= 0.043）室管膜瘤风险增加相关。混合图谱显示，在20p13位点出现峰值，与当地欧洲血统增加有关，而有目标的精细图谱鉴定出rs6039499位点接近rspo4位点的先导变异（优势比= 1.99;95% CI: 1.45-2.73；P= 2.2 × 10−5），但在一组独立的后窝a型患者中未得到验证。结论室管膜瘤风险的种族差异在室管膜瘤患者的基因组祖先中得到了概括，这暗示了未来关联研究的目标区域。
BackgroundEpendymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations.MethodsIn a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS).ResultsCBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08–1.59,Pmeta= 6.7 × 10−3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P= 0.030) and in Hispanics (P= 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 nearRSPO4(odds ratio = 1.99; 95% CI: 1.45–2.73;P= 2.2 × 10−5) but which was not validated in an independent set of posterior fossa type A patients.ConclusionsInterethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies.