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Kinnersley, Ben; Mitchell, Jonathan S.; Gousias, Konstantinos; Schramm, Johannes; Idbaih, Ahmed; Labussiere, Marianne; Marie, Yannick; Rahimian, Amithys; Wichmann, H-Erich; Schreiber, Stefan; Khe Hoang-Xuan; Delattre, Jean-Yves; Noethen, Markus M.; Mokhtari, Karima; Lathrop, Mark; Bondy, Melissa; Simon, Matthias; Sanson, Marc; Houlston, Richard S. (2015): Quantifying the heritability of glioma using genome-wide complex trait analysis. In: Scientific Reports, Vol. 5, 17267


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 x 10(-17)) for all forms of glioma -26% (95% CI: 17-35%,P = 1.05 x 10(-8)) for glioblastoma multiforme (GBM) and 25% (95% CI: 17-32%,P = 1.26 x 10(-10)) for non-GBM tumors. This is a substantial increase from the genetic variance identified by the currently identified GWAS risk loci (similar to 6% of common heritability),indicating that most of the heritable risk attributable to common genetic variants remains to be identified.