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Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma
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نویسنده
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wiggs j.l. ,yaspan b.l. ,hauser m.a. ,kang j.h. ,allingham r.r. ,olson l.m. ,abdrabou w. ,fan b.j. ,wang d.y. ,brodeur w. ,budenz d.l. ,caprioli j. ,crenshaw a. ,crooks k. ,delbono e. ,doheny k.f. ,friedman d.s. ,gaasterland d. ,gaasterland t. ,laurie c. ,lee r.k. ,lichter p.r. ,loomis s. ,liu y. ,medeiros f.a. ,mccarty c. ,mirel d. ,moroi s.e. ,musch d.c. ,realini a. ,rozsa f.w. ,schuman j.s. ,scott k. ,singh k. ,stein j.d. ,trager e.h. ,vanveldhuisen p. ,vollrath d. ,wollstein g. ,yoneyama s. ,zhang k. ,weinreb r.n. ,ernst j. ,kellis m. ,masuda t. ,zack d. ,richards j.e. ,pericak-vance m. ,pasquale l.r. ,haines j.l.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 4
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چکیده
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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 = 1.86×10-18),and the six1/six6 region on chromosome 14q23 (rs10483727 [a],or = 1.32 [95%ci 1.21-1.43],p = 3.87×10-11). 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 = 1.17×10-12) and a probable regulatory region on 8q22 (rs284489 [g],or = 0.62 [95% ci 0.53-0.72],p = 8.88×10-10). 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. © 2012 wiggs et al.
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آدرس
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department of ophthalmology,harvard medical school,massachusetts eye and ear infirmary,boston,ma, United States, vanderbilt university school of medicine,center for human genetics research,nashville,tn, United States, duke university school of medicine,durham,nc, United States, department of medicine and channing laboratory,brigham and women's hospital,boston,ma, United States, duke university school of medicine,durham,nc, United States, vanderbilt university school of medicine,center for human genetics research,nashville,tn, United States, department of ophthalmology,harvard medical school,massachusetts eye and ear infirmary,boston,ma, United States, department of ophthalmology,harvard medical school,massachusetts eye and ear infirmary,boston,ma, United States, department of ophthalmology,harvard medical school,massachusetts eye and ear infirmary,boston,ma, United States, broad institute of harvard and massachusetts institute of technology,boston,ma, United States, department of ophthalmology,university of north carolina school of medicine,durham,nc, United States, department of ophthalmology,university of california los angeles,los angeles,ca, United States, broad institute of harvard and massachusetts institute of technology,boston,ma, United States, duke university school of medicine,durham,nc, United States, department of ophthalmology,harvard medical school,massachusetts eye and ear infirmary,boston,ma, United States, center for inherited disease research,johns hopkins school of medicine,baltimore,md, United States, department of ophthalmology,johns hopkins university school of medicine,baltimore,md, United States, eye doctors of washington d.c.,washington d.c., United States, institute for genomic medicine and marine biology research division,university of california san diego,san diego,ca, United States, department of biostatistics,university of washington,seattle,wa, United States, department of ophthalmology,university of miami,miami,fl, United States, department of ophthalmology and visual sciences,university of michigan,ann arbor,mi, United States, department of ophthalmology,harvard medical school,massachusetts eye and ear infirmary,boston,ma,united states,department of medicine and channing laboratory,brigham and women's hospital,boston,ma, United States, duke university school of medicine,durham,nc, United States, department of ophthalmology,university of california san diego,san diego,ca, United States, essentia institute of rural health,duluth,mn, United States, broad institute of harvard and massachusetts institute of technology,boston,ma, United States, department of ophthalmology and visual sciences,university of michigan,ann arbor,mi, United States, department of ophthalmology and visual sciences,university of michigan,ann arbor,mi,united states,department of epidemiology,university of michigan,ann arbor,mi, United States, department of ophthalmology,west virginia university school of medicine,morgantown,wv, United States, department of ophthalmology and visual sciences,university of michigan,ann arbor,mi, United States, department of ophthalmology,university of pittsburgh,pittsburgh,pa, United States, department of ophthalmology and visual sciences,university of michigan,ann arbor,mi, United States, department of ophthalmology,stanford university,palo alto,ca, United States, department of ophthalmology and visual sciences,university of michigan,ann arbor,mi, United States, department of ophthalmology and visual sciences,university of michigan,ann arbor,mi, United States, the emmes corporation,rockville,md, United States, department of genetics,stanford university,palo alto,ca, United States, department of ophthalmology,university of pittsburgh,pittsburgh,pa, United States, department of ophthalmology and visual sciences,university of michigan,ann arbor,mi,united states,department of epidemiology,university of michigan,ann arbor,mi, United States, department of ophthalmology,university of california san diego,san diego,ca, United States, department of ophthalmology,university of california san diego,san diego,ca, United States, broad institute of harvard and massachusetts institute of technology,boston,ma,united states,computer science and artificial intelligence laboratory,massachusetts institute of technology,cambridge,ma, United States, broad institute of harvard and massachusetts institute of technology,boston,ma,united states,computer science and artificial intelligence laboratory,massachusetts institute of technology,cambridge,ma, United States, department of ophthalmology,johns hopkins university school of medicine,baltimore,md, United States, department of ophthalmology,johns hopkins university school of medicine,baltimore,md, United States, department of ophthalmology and visual sciences,university of michigan,ann arbor,mi,united states,department of epidemiology,university of michigan,ann arbor,mi, United States, department of human genetics,university of miami school of medicine,miami,fl, United States, department of ophthalmology,harvard medical school,massachusetts eye and ear infirmary,boston,ma,united states,department of medicine and channing laboratory,brigham and women's hospital,boston,ma, United States, vanderbilt university school of medicine,center for human genetics research,nashville,tn, United States
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Authors
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