@article {1364569,
	title = {Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma},
	journal = {PLoS Genet},
	volume = {8},
	number = {4},
	year = {2012},
	month = {2012},
	pages = {e1002654},
	abstract = {Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95\%CI 0.63-0.75], p = 1.86{\texttimes}10$^{-}${\textonesuperior}$^{8}$), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95\%CI 1.21-1.43], p = 3.87{\texttimes}10$^{-}${\textonesuperior}{\textonesuperior}). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95\% CI 0.50-0.67], p = 1.17{\texttimes}10$^{-}${\textonesuperior}{\texttwosuperior}) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95\% CI 0.53-0.72], p = 8.88{\texttimes}10$^{-}${\textonesuperior}$^{0}$). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95\% CI 0.41-0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95\% CI 0.54-1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma.},
	keywords = {Alleles, Chromosomes, Human, Pair 8, Chromosomes, Human, Pair 9, Exfoliation Syndrome, Genome-Wide Association Study, Glaucoma, Open-Angle, Homeodomain Proteins, Humans, Nerve Degeneration, Optic Nerve, Polymorphism, Single Nucleotide, RNA, Long Noncoding, RNA, Untranslated, Transforming Growth Factor beta},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1002654},
	author = {Wiggs, Janey L and Yaspan, Brian L and Hauser, Michael A and Kang, Jae H and Allingham, R Rand and Olson, Lana M and Abdrabou, Wael and Fan, Bao J and Wang, Dan Y and Brodeur, Wendy and Budenz, Donald L and Caprioli, Joseph and Crenshaw, Andrew and Crooks, Kristy and Delbono, Elizabeth and Doheny, Kimberly F and Friedman, David S and Gaasterland, Douglas and Gaasterland, Terry and Laurie, Cathy and Lee, Richard K and Lichter, Paul R and Loomis, Stephanie and Liu, Yutao and Medeiros, Felipe A and McCarty, Cathy and Mirel, Daniel and Moroi, Sayoko E and Musch, David C and Realini, Anthony and Rozsa, Frank W and Schuman, Joel S and Scott, Kathleen and Singh, Kuldev and Stein, Joshua D and Trager, Edward H and Vanveldhuisen, Paul and Vollrath, Douglas and Wollstein, Gadi and Yoneyama, Sachiko and Zhang, Kang and Weinreb, Robert N and Ernst, Jason and Kellis, Manolis and Masuda, Tomohiro and Zack, Don and Richards, Julia E and Pericak-Vance, Margaret and Pasquale, Louis R and Haines, Jonathan L}
}
