Data from: Genome-wide Polygenic Risk Scores Predict Risk of Glioma and Molecular Subtypes

<div> <div> <div> <p><strong>Background</strong>: Polygenic risk scores (PRS) aggregate the contribution of many risk variants to provide a personalized genetic susceptibility profile. Since sample sizes of glioma genome-wide association studies (GWAS) remain modest, there is a need to efficiently capture genetic risk using available data.</p> <p><strong>Methods</strong>: We applied a method based on continuous shrinkage priors (PRS-CS) to model the joint effects of over 1 million common variants on disease risk and compared this to an approach (PRS-CT) that only selects a limited set of independent variants that reach genome-wide significance (P&lt;5&times;10-8). PRS models were trained using GWAS stratified by histological (10,346 cases, 14,687 controls) and molecular subtype (2,632 cases, 2,445 controls), and validated in two independent cohorts.</p> <p><strong>Results</strong>: PRS-CS was generally more predictive than PRS-CT with a median increase in explained variance (R2) of 24% (interquartile range=11-30%) across glioma subtypes. Improvements were pronounced for glioblastoma (GBM), with PRS-CS yielding larger odds ratios (OR) per standard deviation (OR=1.93, P=2.0&times;10-54 vs. OR=1.83, P=9.4&times;10-50) and higher explained variance (R2=2.82% vs. R2=2.56%). Individuals in the 80th percentile of the PRS- CS distribution had significantly higher risk of GBM (0.107%) at age 60 compared to those with average PRS (0.046%, P=2.4&times;10-12). Lifetime absolute risk reached 1.18% for glioma and 0.76% for IDH wildtype tumors for individuals in the 95th PRS percentile. PRS-CS augmented the classification of IDH mutation status in cases when added to demographic factors (AUC=0.839 vs. AUC=0.895, P=6.8&times;10-9).</p> <p><strong>Conclusions</strong>: Genome-wide PRS has potential to enhance the detection of high-risk individuals and help distinguish between prognostic glioma subtypes.</p> <p><strong>Citation</strong>: Nakase T, Guerra GA, Ostrom QT, et al. Genome-wide Polygenic Risk Scores Predict Risk of Glioma and Molecular Subtypes. <em>Neuro-Oncology</em>. Published online June 25, 2024:noae112. doi:10.1093/neuonc/noae112</p> </div> </div> </div>