Risk Variants Associated With Normal Pressure Hydrocephalus

Abstract

Background and ObjectivesLarge-scale genome-wide studies of chronic hydrocephalus have been lacking.We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH). MethodsWe used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records.Patients with NPH were selected based on ICD-10 G91.2 diagnosis.To select patients with idiopathic NPH (iNPH) for sensitivity analysis, we excluded patients with a potentially known etiology of the condition using an algorithm on their disease history.The controls were the remaining non-hydrocephalic participants.For a replication analysis, the NPH cohort from UK Biobank (UKBB) was used. ResultsWe included 1,522 patients with NPH (mean age 72.2 years, 53% women) and 451,091 controls (mean age 60.5 years, 44% women).In the GWAS comparing patients with NPH with the controls, we identified 6 gene regions significantly (p < 5.0e-8) associated with NPH that replicated in a meta-analysis with UKBB (NPH n = 173).The top loci near the following genes were rs7962263, SLCO1A2 (odds ratio [OR] 0.71, 95% CI 0.65-0.78,p = 1.0e-14); rs798495, AMZ1/GNA12 (OR 1.29, 95% CI 1.20-1.39,p = 2.9e-12); rs10828247, MLLT10 (OR 0.77, 95% CI 0.71-0.83,p = 1.5e-11); rs561699566 and rs371919113, CDCA2 (OR 0.76, 95% CI 0.70-0.82,p = 1.5e-11); rs56023709, C16orf95 (OR 1.24, 95% CI 1.16-1.33,p = 3.0e-9); and rs62434144, PLEKHG1 (OR 1.23, 95% CI 1.14-1.32,p = 1.4e-8).In the sensitivity analysis comparing only patients with iNPH (n = 1,055) with the controls (n = 451,091), 4 top loci near