Quantifying the heritability of glioma using genome-wide complex trait analysis.

Authors:
Ben Kinnersley, Jonathan S Mitchell, Konstantinos Gousias, Johannes Schramm, Ahmed Idbaih, Marianne Labussière, Yannick Marie, Amithys Rahimian, H-Erich Wichmann, Stefan Schreiber, Khe Hoang-Xuan, Jean-Yves Delattre, Markus M Nöthen, Karima Mokhtari, Mark Lathrop, Melissa Bondy, Matthias Simon, Marc Sanson, Richard S Houlston
Year of publication:
2015
Volume:
5
Issue:
-
Issn:
2045-2322
Journal title abbreviated:
SCI REP-UK
Journal title long:
Scientific Reports
Impact factor:
4.259
Abstract:
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.