@article {913486,
	title = {Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {11},
	year = {2016},
	month = {2016 Sep 1},
	pages = {5046-5052},
	abstract = {Purpose: 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. Methods: 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. Results: 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 \&lt; 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). Conclusions: 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.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20017},
	author = {Khawaja, Anthony P and Cooke Bailey, Jessica N and Kang, Jae Hee and Allingham, R Rand and Hauser, Michael A and Brilliant, Murray and Budenz, Donald L and Christen, William G and Fingert, John and Gaasterland, Douglas and Gaasterland, Terry and Kraft, Peter and Lee, Richard K and Lichter, Paul R and Liu, Yutao and Medeiros, Felipe and Moroi, Syoko E and Richards, Julia E and Realini, Tony and Ritch, Robert and Schuman, Joel S and Scott, William K and Singh, Kuldev and Sit, Arthur J and Vollrath, Douglas and Wollstein, Gadi and Zack, Donald J and Zhang, Kang and Pericak-Vance, Margaret and Weinreb, Robert N and Haines, Jonathan L and Pasquale, Louis R and Wiggs, Janey L}
}
