title: Copy number variation accuracy in genome-wide association studies.
abstract: OBJECTIVE
  Copy number variations (CNVs) are a major source of alterations among individuals and are a potential risk factor in many diseases. Numerous diseases have been linked to deletions and duplications of these chromosomal segments. Data from genome-wide association studies and other microarrays may be used to identify CNVs by several different computer programs, but the reliability of the results has been questioned.
  
  
  METHODS
  To help researchers reduce the number of false-positive CNVs that need to be followed up with laboratory testing, we evaluated the relative performance of CNVPartition, PennCNV and QuantiSNP, and developed a statistical method for estimating sensitivity and positive predictive values of CNV calls and tested it on 96 duplicate samples in our dataset.
  
  
  RESULTS
  We found that the positive predictive rate increases with the number of probes in the CNV and the size of the CNV, with the highest positive predicted rates in CNVs of at least 500 kb and at least 100 probes. Our analysis also indicates that identifying CNVs reported by multiple programs can greatly improve the reproducibility rate and the positive predicted rate.
  
  
  CONCLUSIONS
  Our methods can be used by investigators to identify CNVs in genome-wide data with greater reliability.
authors.affiliation: Department of Psychiatry, Washington University, St. Louis, MO 63110, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Lin
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Hartz
authors.forename: Jen-Chyong
authors.initials: JC
authors.lastname: Wang
authors.forename: Robert F
authors.initials: RF
authors.lastname: Krueger
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Foroud
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Brooks
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Webb
authors.forename: Victor M
authors.initials: VM
authors.lastname: Hesselbrock
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
mesh_terms: D056915:DNA Copy Number Variations / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012984:Software