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

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.