To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the North West of England, UK and 5,500 control samples from the UK Biobank resource.
One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47e-13, odds ratio = 0.67, allele frequency = 0.52). 9p21.3 is a genome-wide association study association hotspot, and a number of genes are localised to this region, CDKN2B-AS1 and CDKN2A/B, also referred to as the INK4 locus.
Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumourigenesis.