title: Identification of genome-wide copy number variations and a family-based association study of Avellino corneal dystrophy.
abstract: OBJECTIVE
  To determine the association of identified copy number variations (CNVs) in whole genome with the risk of Avellino corneal dystrophy (ACD) in a Korean population.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  A total of 146 patients with ACD and 226 control subjects.
  
  
  METHODS
  A total of 193 trios were genotyped by the Illumina HumanHapCNV370-Duo BeadChip (370,404 markers) (Illumina, Inc., San Diego, CA). The intensity signal (log R ratio) and allelic intensity ratio (B allele frequency) of each marker in all individuals were obtained by Illumina BeadStudio software (Illumina, Inc.). To obtain authentic CNVs in this study, we performed a family-based CNV validation and family-based boundary mapping using the PennCNV algorithm, which incorporates multiple factors, including total log R ratio, B allele frequency, and family information, based on an integrated hidden Markov model.
  
  
  METHODS
  Statistical comparison and identification of CNVs between case and control using family information.
  
  
  RESULTS
  We identified 27,267 individual trio CNVs with a median size of 16.2 kb, aggregated in 2245 CNV regions. Most of the identified trio CNVs in this study showed well-defined CNV boundaries and overlapped with those in the Database of Genomic Variants (DGV) (83.4% in number and 79.2% in length). With the common CNV regions (264 CNV regions >5%), we performed a family-based association test with the risk of ACD.
  
  
  CONCLUSIONS
  Two CNV regions (chr6:29978470-29987783 and chr14:59896944-59916129) were significantly associated with the risk of ACD (P=0.05-0.003 and P=0.008, respectively). This study describes the first results of a genome-wide association analysis of individual CNVs with the risk of ACD and shows that 2 novel CNV loci may be involved in the risk of ACD.
  
  
  BACKGROUND
  The author(s) have no proprietary or commercial interest in any materials discussed in this article.
authors.affiliation: Laboratory of Genomic Diversity, Department of Life Science, Sogang University, Shinsu-dong, Mapo-gu, Seoul, Republic of Korea.
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Chun
authors.forename: Tae Joon
authors.initials: TJ
authors.lastname: Park
authors.forename: Ji-On
authors.initials: JO
authors.lastname: Kim
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Kim
authors.forename: Miey
authors.initials: M
authors.lastname: Park
authors.forename: Dong-Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Eung Kweon
authors.initials: EK
authors.lastname: Kim
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018570:Risk Assessment