PURPOSE: Age-related macular degeneration (AMD) is a complex disorder of the retina, characterized by drusen, geographic atrophy, and choroidal neovascularization. Cigarette smoking and the genetic variants CFH Y402H, ARMS2 A69S, CFB R32Q, and C3 R102G have been strongly and consistently associated with AMD. Multiple linkage studies have found evidence suggestive of another AMD locus on chromosome 16p12 but the gene responsible has yet to be identified. METHODS: In the initial phase of the study, single-nucleotide polymorphisms (SNPs) across chromosome 16 were examined for linkage and/or association in 575 Caucasian individuals from 148 multiplex and 77 singleton families. Additional variants were tested in an independent dataset of unrelated cases and controls. According to these results, in combination with gene expression data and biological knowledge, five genes were selected for further study: CACNG3, HS3ST4, IL4R, Q7Z6F8, and ITGAM. RESULTS: After genotyping additional tagging SNPs across each gene, the strongest evidence for linkage and association was found within CACNG3 (rs757200 nonparametric LOD* = 3.3, APL (association in the presence of linkage) P = 0.06, and rs2238498 MQLS (modified quasi-likelihood score) P = 0.006 in the families; rs2283550 P = 1.3 × 10(-6), and rs4787924 P = 0.002 in the case-control dataset). After adjusting for known AMD risk factors, rs2283550 remained strongly associated (P = 2.4 × 10(-4)). Furthermore, the association signal at rs4787924 was replicated in an independent dataset (P = 0.035) and in a joint analysis of all the data (P = 0.001). CONCLUSIONS: These results suggest that CACNG3 is the best candidate for an AMD risk gene within the 16p12 linkage peak. More studies are needed to confirm this association and clarify the role of the gene in AMD pathogenesis.
PURPOSE: Age-related macular degeneration (AMD) is a complex disorder of the retina, characterized by drusen, geographic atrophy, and choroidal neovascularization. Cigarette smoking and the genetic variants CFHY402H, ARMS2A69S, CFB R32Q, and C3 R102G have been strongly and consistently associated with AMD. Multiple linkage studies have found evidence suggestive of another AMD locus on chromosome 16p12 but the gene responsible has yet to be identified. METHODS: In the initial phase of the study, single-nucleotide polymorphisms (SNPs) across chromosome 16 were examined for linkage and/or association in 575 Caucasian individuals from 148 multiplex and 77 singleton families. Additional variants were tested in an independent dataset of unrelated cases and controls. According to these results, in combination with gene expression data and biological knowledge, five genes were selected for further study: CACNG3, HS3ST4, IL4R, Q7Z6F8, and ITGAM. RESULTS: After genotyping additional tagging SNPs across each gene, the strongest evidence for linkage and association was found within CACNG3 (rs757200 nonparametric LOD* = 3.3, APL (association in the presence of linkage) P = 0.06, and rs2238498 MQLS (modified quasi-likelihood score) P = 0.006 in the families; rs2283550 P = 1.3 × 10(-6), and rs4787924 P = 0.002 in the case-control dataset). After adjusting for known AMD risk factors, rs2283550 remained strongly associated (P = 2.4 × 10(-4)). Furthermore, the association signal at rs4787924 was replicated in an independent dataset (P = 0.035) and in a joint analysis of all the data (P = 0.001). CONCLUSIONS: These results suggest that CACNG3 is the best candidate for an AMD risk gene within the 16p12 linkage peak. More studies are needed to confirm this association and clarify the role of the gene in AMD pathogenesis.
Authors: D E Weeks; Y P Conley; T S Mah; T O Paul; L Morse; J Ngo-Chang; J P Dailey; R E Ferrell; M B Gorin Journal: Hum Mol Genet Date: 2000-05-22 Impact factor: 6.150
Authors: D E Weeks; Y P Conley; H J Tsai; T S Mah; P J Rosenfeld; T O Paul; A W Eller; L S Morse; J P Dailey; R E Ferrell; M B Gorin Journal: Am J Ophthalmol Date: 2001-11 Impact factor: 5.258
Authors: Stacey B Gabriel; Stephen F Schaffner; Huy Nguyen; Jamie M Moore; Jessica Roy; Brendan Blumenstiel; John Higgins; Matthew DeFelice; Amy Lochner; Maura Faggart; Shau Neen Liu-Cordero; Charles Rotimi; Adebowale Adeyemo; Richard Cooper; Ryk Ward; Eric S Lander; Mark J Daly; David Altshuler Journal: Science Date: 2002-05-23 Impact factor: 47.728
Authors: S Schmidt; A M Saunders; E A Postel; R M Heinis; A Agarwal; W K Scott; J R Gilbert; J G McDowell; A Bazyk; J D Gass; J L Haines; M A Pericak-Vance Journal: Mol Vis Date: 2000-12-31 Impact factor: 2.367
Authors: Kylee L Spencer; Lana M Olson; Brent M Anderson; Nathalie Schnetz-Boutaud; William K Scott; Paul Gallins; Anita Agarwal; Eric A Postel; Margaret A Pericak-Vance; Jonathan L Haines Journal: Hum Mol Genet Date: 2008-03-06 Impact factor: 6.150
Authors: Johanna Jakobsdottir; Yvette P Conley; Daniel E Weeks; Robert E Ferrell; Michael B Gorin Journal: PLoS One Date: 2008-05-21 Impact factor: 3.240
Authors: Nathan G Lambert; Hanan ElShelmani; Malkit K Singh; Fiona C Mansergh; Michael A Wride; Maximilian Padilla; David Keegan; Ruth E Hogg; Balamurali K Ambati Journal: Prog Retin Eye Res Date: 2016-05-06 Impact factor: 21.198
Authors: Ankita Kumari; Abdul Rahaman; Xin-An Zeng; Muhammad Adil Farooq; Yanyan Huang; Runyu Yao; Murtaza Ali; Romana Ishrat; Rafat Ali Journal: Front Neurosci Date: 2022-07-25 Impact factor: 5.152