An exome sequencing pipeline for identifying and genotyping common CNVs associated with disease with application to psoriasis

Motivation: Despite the prevalence of copy number variation (CNV) in the human genome, only a handful of confirmed associations have been reported between common CNVs and complex disease. This may be partially attributed to the difficulty in accurately genotyping CNVs in large cohorts using array-based technologies. Exome sequencing is now widely being applied to case-control cohorts and presents an exciting opportunity to look for common CNVs associated with disease. Results: We developed ExoCNVTest: an exome sequencing analysis pipeline to identify disease-associated CNVs and to generate absolute copy number genotypes at putatively associated loci. Our method re-discovered the LCE3B_LCE3C CNV association with psoriasis (P-value = 5 x 10e-6) while controlling inflation of test statistics (lambda < 1). ExoCNVTest-derived absolute CNV genotypes were 97.4% concordant with PCR-derived genotypes at this locus.