height and BMI were associated with clinical outcome [78]. In breast cancer, the absolute risk increase in carriers of BRCA1 and BRCA2 pathogenic variants depends on breast cancer polygenic risk scores, which might influence clinical decision-making [79]. The joint modelling of common and rare variants for breast cancer risk prediction can now be performed in the risk calculation tool, BOADICEA [80]. Similarly, in schizophrenia, both structural variation and PRS contribute to risk: schizophrenia cases that carry confirmed copy number variants (CNVs) have higher PRS than cases which do not; within carriers of CNVs, schizophrenia cases have higher PRS than controls [81, 82]. Hence, even in the presence of CNVs with high penetrance [83], polygenic scores affect the overall risk of disease and may be relevant to the clinical expression in CNVs associated with multiple phenotypes like the 22q11.2 deletion [84].
