Skip to main content
Open Access Publications from the University of California

Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses.

  • Author(s): Khawaja, Anthony P
  • Cooke Bailey, Jessica N
  • Kang, Jae Hee
  • Allingham, R Rand
  • Hauser, Michael A
  • Brilliant, Murray
  • Budenz, Donald L
  • Christen, William G
  • Fingert, John
  • Gaasterland, Douglas
  • Gaasterland, Terry
  • Kraft, Peter
  • Lee, Richard K
  • Lichter, Paul R
  • Liu, Yutao
  • Medeiros, Felipe
  • Moroi, Syoko E
  • Richards, Julia E
  • Realini, Tony
  • Ritch, Robert
  • Schuman, Joel S
  • Scott, William K
  • Singh, Kuldev
  • Sit, Arthur J
  • Vollrath, Douglas
  • Wollstein, Gadi
  • Zack, Donald J
  • Zhang, Kang
  • Pericak-Vance, Margaret
  • Weinreb, Robert N
  • Haines, Jonathan L
  • Pasquale, Louis R
  • Wiggs, Janey L
  • et al.


Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins.


We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure.


We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P = 0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P < 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010).


We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View