Logo image
Back
Assessing the association of mitochondrial genetic variation with primary open-angle glaucoma using gene-set analyses
Journal article   Open access   Peer reviewed

Assessing the association of mitochondrial genetic variation with primary open-angle glaucoma using gene-set analyses

Anthony P Khawaja, Jessica N Cooke Bailey, Jonathan L Haines, Jae Hee Kang, Louis R Pasquale, R Rand Allingham, Michael A Hauser, Murray Brilliant, Donald L Budenz, William G Christen, …
Investigative Ophthalmology and Visual Science, Vol.57(11), pp.5046-5052
2016
DOI: 10.1167/iovs.16-20017
PMCID: PMC5040191
PMID: 27661856
url
https://doi.org/10.1167/iovs.16-20017View
Published (Version of record) Open Access

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 < 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.

Details

Metrics

42 Record Views
51 Times Cited - Web of Science
Logo image