title: DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma.
abstract: OBJECTIVE
  We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG).
  
  
  METHODS
  Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non-blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those ≥5 kilobases (kb) in size and interrogated by ≥5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC.
  
  
  RESULTS
  Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls.
  
  
  CONCLUSIONS
  The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation.
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia, United States Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States.
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Garrett
authors.affiliation: Genentech, Inc., San Francisco, California, United States.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Yaspan
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Jessica Cooke
authors.initials: JC
authors.lastname: Bailey
authors.affiliation: Department of Ophthalmology, Massachusetts Eye & Ear, Boston, Massachusetts, United States.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Loomis
authors.affiliation: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, United States.
authors.forename: Murray
authors.initials: M
authors.lastname: Brilliant
authors.affiliation: Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, United States.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Budenz
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States.
authors.forename: William G
authors.initials: WG
authors.lastname: Christen
authors.affiliation: Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States.
authors.forename: John H
authors.initials: JH
authors.lastname: Fingert
authors.affiliation: Eye Doctors of Washington, Chevy Chase, Maryland, United States.
authors.forename: Douglas
authors.initials: D
authors.lastname: Gaasterland
authors.affiliation: Scripps Genome Center, University of California at San Diego, San Diego, California, United States.
authors.forename: Terry
authors.initials: T
authors.lastname: Gaasterland
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States.
authors.forename: Jae H
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Lichter
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Sayoko E
authors.initials: SE
authors.lastname: Moroi
authors.affiliation: Department of Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, United States;
authors.forename: Anthony
authors.initials: A
authors.lastname: Realini
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Richards
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Schuman
authors.affiliation: Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States.
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.affiliation: Department of Ophthalmology, Stanford University, Palo Alto, California, United States.
authors.forename: Kuldev
authors.initials: K
authors.lastname: Singh
authors.affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Sit
authors.affiliation: Department of Ophthalmology, Stanford University, Palo Alto, California, United States.
authors.forename: Douglas
authors.initials: D
authors.lastname: Vollrath
authors.affiliation: Department of Ophthalmology and Hamilton Glaucoma Center, University of California, San Diego, California, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Weinreb
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
authors.forename: Gadi
authors.initials: G
authors.lastname: Wollstein
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland, United States.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Zack
authors.affiliation: Department of Ophthalmology and Hamilton Glaucoma Center, University of California, San Diego, California, United States.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.affiliation: Department of Ophthalmology, Massachusetts Eye & Ear, Boston, Massachusetts, United States Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
authors.affiliation: Department of Ophthalmology, Massachusetts Eye & Ear, Boston, Massachusetts, United States.
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States.
authors.forename: Allison E
authors.initials: AE
authors.lastname: Ashley-Koch
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D005136:Eye Proteins
keywords: DNA copy number variants; GAS7; POAG; SIX6; genetics