Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus

Autoria(s): Strange, A.; Bellenguez, C.; Sim, X.; Luben, R.; Hysi, P. G.; Ramdas, W. D.; van Koolwijk, L. M.; Freeman, C.; Pirinen, M.; Su, Z.; Band, G.; Pearson, R.; Vukcevic, D.; Langford, C.; Deloukas, P.; Hunt, S.; Gray, E.; Dronov, S.; Potter, S. C.; Tashakkori-Ghanbaria, A.; Edkins, S.; Bumpstead, S. J.; Blackwell, J. M.; Bramon, E.; Brown, Matthew A.; Casas, J. P.; Corvin, A.; Duncanson, A.; Jankowski, J. A.; Markus, H. S.; Mathew, C. G.; Palmer, C. N.; Plomin, R.; Rautanen, A.; Sawcer, S. J.; Trembath, R. C.; Wood, N. W.; Barroso, I.; Leena Peltonen, L. P.; Healey, P.; McGuffin, P.; Topouzis, F.; Klaver, C. C.; van Duijn, C. M.; Mackey, D. A.; Young, T. L.; Hammond, C. J.; Khaw, K. T.; Wareham, N.; Wang, J. J.; Wong, T. Y.; Foster, P. J.; Mitchell, P.; Spencer, C. C.; Donnelly, P.; Viswanathan, A. C.
Data(s)

2013
Resumo

To discover quantitative trait loci for intraocular pressure, amajor risk factor for glaucoma and the only modifiable one,weperformed agenome-wide association studyonadiscoverycohort of2175individualsfromSydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, Pcombined = 1.10 × 10-8). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30-0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.
Identificador

http://eprints.qut.edu.au/89275/
Publicador

Oxford University Press
Relação

DOI:10.1093/hmg/ddt293

Strange, A., Bellenguez, C., Sim, X., Luben, R., Hysi, P. G., Ramdas, W. D., van Koolwijk, L. M., Freeman, C., Pirinen, M., Su, Z., Band, G., Pearson, R., Vukcevic, D., Langford, C., Deloukas, P., Hunt, S., Gray, E., Dronov, S., Potter, S. C., Tashakkori-Ghanbaria, A., Edkins, S., Bumpstead, S. J., Blackwell, J. M., Bramon, E., Brown, Matthew A., Casas, J. P., Corvin, A., Duncanson, A., Jankowski, J. A., Markus, H. S., Mathew, C. G., Palmer, C. N., Plomin, R., Rautanen, A., Sawcer, S. J., Trembath, R. C., Wood, N. W., Barroso, I., Leena Peltonen, L. P., Healey, P., McGuffin, P., Topouzis, F., Klaver, C. C., van Duijn, C. M., Mackey, D. A., Young, T. L., Hammond, C. J., Khaw, K. T., Wareham, N., Wang, J. J., Wong, T. Y., Foster, P. J., Mitchell, P., Spencer, C. C., Donnelly, P., & Viswanathan, A. C. (2013) Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus. Human Molecular Genetics, 22(22), pp. 4653-4660.
Direitos

Copyright 2013 The Authors
Fonte

Faculty of Health; Institute of Health and Biomedical Innovation
Palavras-Chave #GLCCI1 protein #ICA1 protein #protein #unclassified drug #adult #aged #allele #article #Australia #cohort analysis #female #gene locus #genetic association #genetic susceptibility #genetic variability #genotype #human #intraocular pressure #major clinical study #male #open angle glaucoma #priority journal #quantitative trait locus #single nucleotide polymorphism #Alleles #Autoantigens #Chromosomes #Human #Pair 7 #Cohort Studies #Genetic Predisposition to Disease #Genetic Variation #Genome-Wide Association Study #Glaucoma #Open-Angle #Humans #Middle Aged #Polymorphism #Single Nucleotide #Prospective Studies #Quantitative Trait Loci #Receptors #Glucocorticoid #Risk Factors
Tipo

Journal Article
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