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Abstract #58782 Published in IGR 16-3
Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma
Bailey JN; Yaspan BL; Pasquale LR; Hauser MA; Kang JH; Loomis SJ; Brilliant M; Budenz DL; Christen WG; Fingert J; Gaasterland D; Gaasterland T; Kraft P; Lee RK; Lichter PR; Liu Y; McCarty CA; Moroi SE; Richards JE; Realini T; Schuman JS; Scott WK; Singh KHuman Genetics 2014; 133: 1319-1330
Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Using genome-wide association single-nucleotide polymorphism data from the Glaucoma Genes and Environment study and National Eye Institute Glaucoma Human Genetics Collaboration comprising 3,108 cases and 3,430 controls, we assessed biologic pathways as annotated in the KEGG database for association with risk of POAG. After correction for genic overlap among pathways, we found 4 pathways, butanoate metabolism (hsa00650), hematopoietic cell lineage (hsa04640), lysine degradation (hsa00310) and basal transcription factors (hsa03022) related to POAG with permuted p < 0.001. In addition, the human leukocyte antigen (HLA) gene family was significantly associated with POAG (p < 0.001). In the POAG subset with normal-pressure glaucoma (NPG), the butanoate metabolism pathway was also significantly associated (p < 0.001) as well as the MAPK and Hedgehog signaling pathways (hsa04010 and hsa04340), glycosaminoglycan biosynthesis-heparan sulfate pathway (hsa00534) and the phenylalanine, tyrosine and tryptophan biosynthesis pathway (hsa0400). The butanoate metabolism pathway overall, and specifically the aspects of the pathway that contribute to GABA and acetyl-CoA metabolism, was the only pathway significantly associated with both POAG and NPG. Collectively these results implicate GABA and acetyl-CoA metabolism in glaucoma pathogenesis, and suggest new potential therapeutic targets.
Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA.
Full articleClassification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
9.2.4 Normal pressure glaucoma (Part of: 9 Clinical forms of glaucomas > 9.2 Primary open angle glaucomas)
1.3 Pathogenesis (Part of: 1 General aspects)
