title: Genome-wide CNV analysis replicates the association between GSTM1 deletion and bladder cancer: a support for using continuous measurement from SNP-array data.
abstract: BACKGROUND
  Structural variations such as copy number variants (CNV) influence the expression of different phenotypic traits. Algorithms to identify CNVs through SNP-array platforms are available. The ability to evaluate well-characterized CNVs such as GSTM1 (1p13.3) deletion provides an important opportunity to assess their performance.
  
  
  RESULTS
  773 cases and 759 controls from the SBC/EPICURO Study were genotyped in the GSTM1 region using TaqMan, Multiplex Ligation-dependent Probe Amplification (MLPA), and Illumina Infinium 1 M SNP-array platforms. CNV callings provided by TaqMan and MLPA were highly concordant and replicated the association between GSTM1 and bladder cancer. This was not the case when CNVs were called using Illumina 1 M data through available algorithms since no deletion was detected across the study samples. In contrast, when the Log R Ratio (LRR) was used as a continuous measure for the 5 probes contained in this locus, we were able to detect their association with bladder cancer using simple regression models or more sophisticated methods such as the ones implemented in the CNVtools package.
  
  
  CONCLUSIONS
  This study highlights an important limitation in the CNV calling from SNP-array data in regions of common aberrations and suggests that there may be added advantage for using LRR as a continuous measure in association tests rather than relying on calling algorithms.
authors: Spanish National Cancer Research Center (CNIO), Madrid, E-28029, Spain.
authors: Gaëlle
authors: G
authors: Marenne
authors: Francisco X
authors: FX
authors: Real
authors: Nathaniel
authors: N
authors: Rothman
authors: Benjamin
authors: B
authors: Rodríguez-Santiago
authors: Luis
authors: L
authors: Pérez-Jurado
authors: Manolis
authors: M
authors: Kogevinas
authors: Montse
authors: M
authors: García-Closas
authors: Debra T
authors: DT
authors: Silverman
authors: Stephen J
authors: SJ
authors: Chanock
authors: Emmanuelle
authors: E
authors: Génin
authors: Núria
authors: N
authors: Malats
mesh_terms: D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D030541:Databases, Genetic; D017353:Gene Deletion; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics*
chemical_list: D005982:Glutathione Transferase