Fig. 1

Systematic analysis of the enrichment of rare pathogenic variants in cases compared to control samples. a Proposed hypothesis that rare pathogenic variants in Mendelian disease-associated genes (OMIM genes) increase the risk of cancer. b Overview of the case–control analysis. Principal components analysis (PCA) using common variants was performed to stratify the population of cases (cancer patients) and control individuals. After defining pathogenic variants (PTVs or ClinVar pathogenic variants) from case–control samples, the linear regression model tests germline variant enrichments in cases compared to controls with the first four PC values. AFR: African, AMR: American, EAS: East Asian, EUR: European, and SAS: South Asian