title: Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism.
abstract: BACKGROUND
  Copy number variation (CNV) is a potential contributing factor to many genetic diseases. Here we investigated the potential association of CNV with nonsyndromic cryptorchidism, the most common male congenital genitourinary defect, in a Caucasian population.
  
  
  METHODS
  Genome wide genotyping were performed in 559 cases and 1772 controls (Group 1) using Illumina HumanHap550 v1, HumanHap550 v3 or Human610-Quad platforms and in 353 cases and 1149 controls (Group 2) using the Illumina Human OmniExpress 12v1 or Human OmniExpress 12v1-1. Signal intensity data including log R ratio (LRR) and B allele frequency (BAF) for each single nucleotide polymorphism (SNP) were used for CNV detection using PennCNV software. After sample quality control, gene- and CNV-based association tests were performed using cleaned data from Group 1 (493 cases and 1586 controls) and Group 2 (307 cases and 1102 controls) using ParseCNV software. Meta-analysis was performed using gene-based test results as input to identify significant genes, and CNVs in or around significant genes were identified in CNV-based association test results. Called CNVs passing quality control and signal intensity visualization examination were considered for validation using TaqMan CNV assays and QuantStudio® 3D Digital PCR System.
  
  
  RESULTS
  The meta-analysis identified 373 genome wide significant (p < 5X10-4) genes/loci including 49 genes/loci with deletions and 324 with duplications. Among them, 17 genes with deletion and 1 gene with duplication were identified in CNV-based association results in both Group 1 and Group 2. Only 2 genes (NUCB2 and UPF2) containing deletions passed CNV quality control in both groups and signal intensity visualization examination, but laboratory validation failed to verify these deletions.
  
  
  CONCLUSIONS
  Our data do not support that structural variation is a major cause of nonsyndromic cryptorchidism.
authors: Nemours Biomedical Research, Nemours /Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
authors: Yanping
authors: Y
authors: Wang
authors: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
authors: Jin
authors: J
authors: Li
authors: Division of Urology, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
authors: Thomas F
authors: TF
authors: Kolon
authors: Nemours Biomedical Research, Nemours /Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
authors: Alicia
authors: A
authors: Olivant Fisher
authors: Division of Urology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
authors: T Ernesto
authors: TE
authors: Figueroa
authors: Division of Urology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
authors: Ahmad H
authors: AH
authors: BaniHani
authors: Division of Urology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
authors: Jennifer A
authors: JA
authors: Hagerty
authors: Division of Urology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.|Present address: Auf der Bult Kinder- und Jugendkrankenhaus, Hannover, Germany.
authors: Ricardo
authors: R
authors: Gonzalez
authors: Division of Urology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.|Present address: Division of Pediatric Urology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: Paul H
authors: PH
authors: Noh
authors: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
authors: Rosetta M
authors: RM
authors: Chiavacci
authors: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
authors: Kisha R
authors: KR
authors: Harden
authors: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
authors: Debra J
authors: DJ
authors: Abrams
authors: Nemours Biomedical Research, Nemours /Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
authors: Deborah
authors: D
authors: Stabley
authors: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
authors: Cecilia E
authors: CE
authors: Kim
authors: Nemours Biomedical Research, Nemours /Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
authors: Katia
authors: K
authors: Sol-Church
authors: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.|Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors: Hakon
authors: H
authors: Hakonarson
authors: Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.|Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.|Department of Molecular Medicine, Sapienza University, Rome, Italy.
authors: Marcella
authors: M
authors: Devoto
authors: Nemours Biomedical Research, Nemours /Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA. Julia.Barthold@nemours.org.|Division of Urology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA. Julia.Barthold@nemours.org.
authors: Julia Spencer
authors: JS
authors: Barthold
mesh_terms: D003456:Cryptorchidism / Q000235:genetics*; D056915:DNA Copy Number Variations; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D012984:Software; D044465:White People / Q000235:genetics*
keywords: CNV; Cryptorchidism; Genetics