Rare Modifier Variants Alter the Severity of Cardiovascular Disease in Pseudoxanthoma Elasticum: Identification of Novel Candidate Modifier Genes and Disease Pathways Through Mixture of Effects Analysis

Mixed effects of rare variants were assessed by Whole Exome Sequencing in 11 PXE patients with an extreme CV phenotype (mild/severe). Statistical analysis (SKAT-O and C-alpha testing) was performed to identify new modifier genes for the CV PXE phenotype and enrichment analysis for genes significantly associated with the severe cohort was used to evaluate pathway and gene ontology features.