Assessment of copy number variation using the Illumina Infinium 1M SNP-array: a comparison of methodological approaches in the Spanish Bladder Cancer/EPICURO study

Abstract

High‐throughput single nucleotide polymorphism (SNP)‐array technologies allow to investigate copy number variants (CNVs) in genome‐wide scans and specific calling algorithms have been developed to determine CNV location and copy number. We report the results of a reliability analysis comparing data from 96 pairs of samples processed with CNVpartition, PennCNV, and QuantiSNP for Infinium Illumina Human 1Million probe chip data. We also performed a validity assessment with multiplex ligation‐dependent probe amplification (MLPA) as a reference standard. The number of CNVs per individual varied according to the calling algorithm. Higher numbers of CNVs were detected in saliva than in blood DNA samples regardless of the algorithm used. All algorithms presented low agreement with mean Kappa Index (KI) 0.62). Our results indicate that the current calling algorithms should be improved for high performance CNV analysis in genome‐wide scans. Further refinement is required to assess CNVs as risk factors in complex diseases.Hum Mutat 32:1–10, 2011.