DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma

Yutao Liu, Melanie E. Garrett, Brian L. Yaspan, Jessica Cooke Bailey, Stephanie J. Loomis, Murray Brilliant, Donald L. Budenz, William G. Christen, John H. Fingert, Douglas Gaasterland, Terry Gaasterland, Jae H. Kang, Richard K. Lee, Paul Lichter, Sayoko E. Moroi, Anthony Realini, Julia E. Richards, Joel S. Schuman, William K. Scott, Kuldev SinghArthur J. Sit, Douglas Vollrath, Robert Weinreb, Gadi Wollstein, Donald J. Zack, Kang Zhang, Margaret A. Pericak-Vance, Jonathan L. Haines, Louis R. Pasquale, Janey L. Wiggs, R. Rand Allingham, Allison E. Ashley-Koch, Michael A. Hauser

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Purpose: 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.

Original languageEnglish (US)
Pages (from-to)8251-8258
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number12
StatePublished - Nov 20 2014


  • DNA copy number variants
  • GAS7
  • Genetics
  • POAG
  • SIX6

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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