Kinnersley Ben, Mitchell Jonathan S, Gousias Konstantinos, Schramm Johannes, Idbaih Ahmed, Labussière Marianne, Marie Yannick, Rahimian Amithys, Wichmann H-Erich, Schreiber Stefan, Hoang-Xuan Khe, Delattre Jean-Yves, Nöthen Markus M, Mokhtari Karima, Lathrop Mark, Bondy Melissa, Simon Matthias, Sanson Marc, Houlston Richard S
Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Sci Rep. 2015 Dec 2;5:17267. doi: 10.1038/srep17267.
Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) influencing glioma risk. While these SNPs only explain a small proportion of the genetic risk it is unclear how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we applied Genome-Wide Complex Trait Analysis (GCTA) to three GWAS datasets totalling 3,373 cases and 4,571 controls and performed a meta-analysis to estimate the heritability of glioma. Our results identify heritability estimates of 25% (95% CI: 20-31%, P = 1.15 × 10(-17)) for all forms of glioma - 26% (95% CI: 17-35%, P = 1.05 × 10(-8)) for glioblastoma multiforme (GBM) and 25% (95% CI: 17-32%, P = 1.26 × 10(-10)) for non-GBM tumors. This is a substantial increase from the genetic variance identified by the currently identified GWAS risk loci (~6% of common heritability), indicating that most of the heritable risk attributable to common genetic variants remains to be identified.
全基因组关联研究（GWAS）已成功识别出一些影响胶质瘤风险的常见单核苷酸多态性（SNP）。虽然这些SNP仅解释了一小部分遗传风险，但尚不清楚其他有待识别的常见SNP还能检测出多少风险。因此，我们将全基因组复杂性状分析（GCTA）应用于三个GWAS数据集，共计3373例病例和4571例对照，并进行了荟萃分析以估计胶质瘤的遗传度。我们的结果显示，所有形式的胶质瘤的遗传度估计值为25%（95%置信区间：20 - 31%，P = 1.15×10⁻¹⁷）——多形性胶质母细胞瘤（GBM）为26%（95%置信区间：17 - 35%，P = 1.05×10⁻⁸），非GBM肿瘤为25%（95%置信区间：17 - 32%，P = 1.26×10⁻¹⁰）。这比目前已识别的GWAS风险位点所确定的遗传方差（约占常见遗传度的6%）有大幅增加，表明大部分可归因于常见遗传变异的遗传风险仍有待识别。
