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Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma.

Publication ,  Journal Article
Bailey, JNC; Yaspan, BL; Pasquale, LR; Hauser, MA; Kang, JH; Loomis, SJ; Brilliant, M; Budenz, DL; Christen, WG; Fingert, J; Gaasterland, D ...
Published in: Hum Genet
October 2014

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.

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Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

October 2014

Volume

133

Issue

10

Start / End Page

1319 / 1330

Location

Germany

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Polymorphism, Single Nucleotide
  • Models, Genetic
  • Metabolic Networks and Pathways
  • Male
  • Intraocular Pressure
  • Humans
  • Glaucoma, Open-Angle
  • Glaucoma
  • Genetics & Heredity
 

Citation

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Bailey, J. N. C., Yaspan, B. L., Pasquale, L. R., Hauser, M. A., Kang, J. H., Loomis, S. J., … Wiggs, J. L. (2014). Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma. Hum Genet, 133(10), 1319–1330. https://doi.org/10.1007/s00439-014-1468-7
Bailey, Jessica N Cooke, Brian L. Yaspan, Louis R. Pasquale, Michael A. Hauser, Jae H. Kang, Stephanie J. Loomis, Murray Brilliant, et al. “Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma.Hum Genet 133, no. 10 (October 2014): 1319–30. https://doi.org/10.1007/s00439-014-1468-7.
Bailey JNC, Yaspan BL, Pasquale LR, Hauser MA, Kang JH, Loomis SJ, et al. Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma. Hum Genet. 2014 Oct;133(10):1319–30.
Bailey, Jessica N. Cooke, et al. “Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma.Hum Genet, vol. 133, no. 10, Oct. 2014, pp. 1319–30. Pubmed, doi:10.1007/s00439-014-1468-7.
Bailey JNC, 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 K, Sit AJ, Vollrath D, Wollstein G, Zack DJ, Zhang K, Pericak-Vance MA, Allingham RR, Weinreb RN, Haines JL, Wiggs JL. Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma. Hum Genet. 2014 Oct;133(10):1319–1330.
Journal cover image

Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

October 2014

Volume

133

Issue

10

Start / End Page

1319 / 1330

Location

Germany

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Polymorphism, Single Nucleotide
  • Models, Genetic
  • Metabolic Networks and Pathways
  • Male
  • Intraocular Pressure
  • Humans
  • Glaucoma, Open-Angle
  • Glaucoma
  • Genetics & Heredity