Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity

Highlights: • Epistasis aware polygenic risk scores (PRSs) can predict late radiotherapy toxicity. • SNP-SNP interactions can be summarized to foster interpretability. • Allele combinations may be more informative with respect to single genetic variants. • Our interaction-aware score outperforms classical PRSs. To identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi).