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Research Article

Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

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Pages 77-93 | Received 21 Jun 2010, Accepted 29 Mar 2011, Published online: 24 May 2011

REFERENCES

  • Silvestri G, Johnston PB, Hughes AE. Is genetic predisposition an important risk factor in age-related macular degeneration? Eye (Lond). 1994;8 (Pt 5):564–568.
  • Seddon JM, Ajani UA, Mitchell BD. Familial aggregation of age-related maculopathy. Am. J. Ophthalmol. 1997;123(2):199–206.
  • Klaver CC, Wolfs RC, Assink JJ, et al. Genetic risk of age-related maculopathy. Population-based familial aggregation study. Arch. Ophthalmol. 1998;116(12):1646–1651.
  • Swaroop A, Branham KE, Chen W, Abecasis G. Genetic susceptibility to age-related macular degeneration: A paradigm for dissecting complex disease traits. Hum. Mol. Genet. 2007;16 Spec No. 2:R174–182.
  • Hammond CJ, Webster AR, Snieder H, et al. Genetic influence on early age-related maculopathy: A twin study. Ophthalmology. 2002;109(4):730–736.
  • Friedman DS, O’Colmain BJ, Muñoz B, et al. Prevalence of age-related macular degeneration in the United States. Arch. Ophthalmol. 2004;122(4):564–572.
  • Ferris FL, Davis MD, Clemons TE, et al. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Arch. Ophthalmol. 2005;123(11):1570–1574.
  • Swaroop A, Chew EY, Rickman CB, Abecasis GR. Unraveling a multifactorial late-onset disease: From genetic susceptibility to disease mechanisms for age-related macular degeneration. Annu Rev Genomics Hum Genet. 2009;10:19–43.
  • Jakobsdottir J, Gorin MB, Conley YP, Ferrell RE, Weeks DE. Interpretation of genetic association studies: Markers with replicated highly significant odds ratios may be poor classifiers. PLoS Genet. 2009;5(2):e1000337.
  • Friedman DS, Katz J, Bressler NM, Rahmani B, Tielsch JM. Racial differences in the prevalence of age-related macular degeneration: The Baltimore Eye Survey. Ophthalmology. 1999;106(6):1049–1055.
  • VanNewkirk MR, Nanjan MB, Wang JJ, et al. The prevalence of age-related maculopathy: The visual impairment project. Ophthalmology. 2000;107(8):1593–1600.
  • Muñoz B, Klein R, Rodriguez J, Snyder R, West SK. Prevalence of age-related macular degeneration in a population-based sample of Hispanic people in Arizona: Proyecto VER. Arch. Ophthalmol. 2005;123(11):1575–1580.
  • Thornton J, Edwards R, Mitchell P, et al. Smoking and age-related macular degeneration: A review of association. Eye (Lond). 2005;19(9):935–944.
  • Klein R. Overview of progress in the epidemiology of age-related macular degeneration. Ophthalmic Epidemiol. 2007;14(4):184–187.
  • Cruickshanks KJ, Klein R, Klein BE, Nondahl DM. Sunlight and the 5-year incidence of early age-related maculopathy: The beaver dam eye study. Arch. Ophthalmol. 2001;119(2):246–250.
  • Taylor HR, Muñoz B, West S, et al. Visible light and risk of age-related macular degeneration. Trans Am Ophthalmol Soc. 1990;88:163–173; discussion 173–178.
  • Delcourt C, Carrière I, Ponton-Sanchez A, et al. Light exposure and the risk of age-related macular degeneration: The Pathologies Oculaires Liées à l’Age (POLA) study. Arch. Ophthalmol. 2001;119(10):1463–1468.
  • Hyman LG, Lilienfeld AM, Ferris FL, Fine SL. Senile macular degeneration: A case-control study. Am. J. Epidemiol. 1983;118(2):213–227.
  • West SK, Duncan DD, Muñoz B, et al. Sunlight exposure and risk of lens opacities in a population-based study: The Salisbury Eye Evaluation project. JAMA. 1998;280(8):714–718.
  • Jakobsdottir J, Conley YP, Weeks DE, et al. Susceptibility genes for age-related maculopathy on chromosome 10q26. Am. J. Hum. Genet. 2005;77(3):389–407.
  • Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308(5720):385–389.
  • Haines JL, Hauser MA, Schmidt S, et al. Complement factor H variant increases the risk of age-related macular degeneration. Science. 2005;308(5720):419–421.
  • Edwards AO, Ritter R, Abel KJ, et al. Complement factor H polymorphism and age-related macular degeneration. Science. 2005;308(5720):421–424.
  • Hageman GS, Anderson DH, Johnson LV, et al. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 2005;102(20):7227–7232.
  • Rivera A, Fisher SA, Fritsche LG, et al. Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. Hum. Mol. Genet. 2005;14(21):3227–3236.
  • Dewan A, Liu M, Hartman S, et al. HTRA1 promoter polymorphism in wet age-related macular degeneration. Science. 2006;314(5801):989–992.
  • Li M, Atmaca-Sonmez P, Othman M, et al. CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration. Nat. Genet. 2006;38(9):1049–1054.
  • Yang Z, Camp NJ, Sun H, et al. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 2006;314(5801):992–993.
  • DeAngelis MM, Ji F, Kim IK, et al. Cigarette smoking, CFH, APOE, ELOVL4, and risk of neovascular age-related macular degeneration. Arch. Ophthalmol. 2007;125(1):49–54.
  • Fisher SA, Abecasis GR, Yashar BM, et al. Meta-analysis of genome scans of age-related macular degeneration. Hum. Mol. Genet. 2005;14(15):2257–2264.
  • Shuler RK, Hauser MA, Caldwell J, et al. Neovascular age-related macular degeneration and its association with LOC387715 and complement factor H polymorphism. Arch. Ophthalmol. 2007;125(1):63–67.
  • Zhang H, Morrison MA, Dewan A, et al. The NEI/NCBI dbGAP database: Genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration. BMC Med. Genet. 2008;9:51.
  • Klein ML, Schultz DW, Edwards A, et al. Age-related macular degeneration. Clinical features in a large family and linkage to chromosome 1q. Arch. Ophthalmol. 1998;116(8):1082–1088.
  • Majewski J, Schultz DW, Weleber RG, et al. Age-related macular degeneration–A genome scan in extended families. Am. J. Hum. Genet. 2003;73(3):540–550.
  • Schick JH, Iyengar SK, Klein BE, et al. A whole-genome screen of a quantitative trait of age-related maculopathy in sibships from the Beaver Dam Eye Study. Am. J. Hum. Genet. 2003;72(6):1412–1424.
  • Abecasis GR, Yashar BM, Zhao Y, et al. Age-related macular degeneration: A high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease. Am. J. Hum. Genet. 2004;74(3):482–494.
  • Iyengar SK, Song D, Klein BEK, et al. Dissection of genomewide-scan data in extended families reveals a major locus and oligogenic susceptibility for age-related macular degeneration. Am. J. Hum. Genet. 2004;74(1):20–39.
  • Schmidt S, Scott WK, Postel EA, et al. Ordered subset linkage analysis supports a susceptibility locus for age-related macular degeneration on chromosome 16p12. BMC Genet. 2004;5:18.
  • Kenealy SJ, Schmidt S, Agarwal A, et al. Linkage analysis for age-related macular degeneration supports a gene on chromosome 10q26. Mol. Vis. 2004;10:57–61.
  • Jun G, Klein BEK, Klein R, et al. Genome-wide analyses demonstrate novel loci that predispose to drusen formation. Invest. Ophthalmol. Vis. Sci. 2005;46(9):3081–3088.
  • Silveira AC, Morrison MA, Ji F, et al. Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: A systems biology based approach. Vision Res. 2010;50(7):698–715.
  • St George-Hyslop P, Haines J, Rogaev E, et al. Genetic evidence for a novel familial Alzheimer’s disease locus on chromosome 14. Nat. Genet. 1992;2(4):330–334.
  • Rogaev EI, Sherrington R, Rogaeva EA, et al. Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature. 1995;376(6543):775–778.
  • Kennedy JL, Farrer LA, Andreasen NC, Mayeux R, St George-Hyslop P. The genetics of adult-onset neuropsychiatric disease: Complexities and conundra? Science. 2003;302(5646):822–826.
  • Yu P, Oberto G. Alzheimer’s disease: Transgenic mouse models and drug assessment. Pharmacol. Res. 2000;42(2):107–114.
  • Ishii K, Lippa C, Tomiyama T, et al. Distinguishable effects of presenilin-1 and APP717 mutations on amyloid plaque deposition. Neurobiol. Aging. 2001;22(3):367–376.
  • Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science. 2002;297(5580):353–356.
  • Gold B, Merriam JE, Zernant J, et al. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat. Genet. 2006;38(4):458–462.
  • Maller J, George S, Purcell S, et al. Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nat. Genet. 2006;38(9):1055–1059.
  • Hughes AE, Orr N, Esfandiary H, et al. A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Nat. Genet. 2006;38(10):1173–1177.
  • Yates ?Sepp T, Matharu BK, et al. Complement C3 variant and the risk of age-related macular degeneration. N. Engl. J. Med. 2007;357(6):553–561.
  • Maller JB, Fagerness JA, Reynolds RC, et al. Variation in complement factor 3 is associated with risk of age-related macular degeneration. Nat. Genet. 2007;39(10):1200–1201.
  • Spencer KL, Hauser MA, Olson LM, et al. Protective effect of complement factor B and complement component 2 variants in age-related macular degeneration. Hum. Mol. Genet. 2007;16(16):1986–1992.
  • Jakobsdottir J, Conley YP, Weeks DE, Ferrell RE, Gorin MB. C2 and CFB genes in age-related maculopathy and joint action with CFH and LOC387715 genes. PLoS ONE. 2008;3(5):e2199.
  • Gehrs KM, Jackson JR, Brown EN, Allikmets R, Hageman GS. Complement, age-related macular degeneration and a vision of the future. Arch. Ophthalmol. 2010;128(3):349–358.
  • Chen W, Stambolian D, Edwards AO, et al. Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 2010;107(16):7401–7406.
  • Fagerness JA, Maller JB, Neale BM, et al. Variation near complement factor I is associated with risk of advanced AMD. Eur. J. Hum. Genet. 2009;17(1):100–104.
  • Moonesinghe R, Liu T, Khoury MJ. Evaluation of the discriminative accuracy of genomic profiling in the prediction of common complex diseases. Eur. J. Hum. Genet. 2010;18(4):485–489.
  • Kelly M, Semsarian C. Multiple mutations in genetic cardiovascular disease: A marker of disease severity? Circ Cardiovasc Genet. 2009;2(2):182–190.
  • Ioannidis JPA. Prediction of cardiovascular disease outcomes and established cardiovascular risk factors by genome-wide association markers. Circ Cardiovasc Genet. 2009;2(1):7–15.
  • Lusis AJ, Weiss JN. Cardiovascular networks: Systems-based approaches to cardiovascular disease. Circulation. 2010;121(1):157–170.
  • O’Rahilly S. Human genetics illuminates the paths to metabolic disease. Nature. 2009;462(7271):307–314.
  • Hakonarson H, Grant SFA. Genome-wide association studies in type 1 diabetes, inflammatory bowel disease and other immune-mediated disorders. Semin. Immunol. 2009;21(6):355–362.
  • Reitz C, Mayeux R. Use of genetic variation as biomarkers for Alzheimer’s disease. Ann. N. Y. Acad. Sci. 2009;1180:75–96.
  • Gubitz AK, Gwinn K. Mining the genome for susceptibility to complex neurological disorders. Curr. Mol. Med. 2009;9(7):801–813.
  • Bertram L, Tanzi RE. Genome-wide association studies in Alzheimer’s disease. Hum. Mol. Genet. 2009;18(R2):R137–145.
  • Cichon S, Craddock N, Daly M, et al. Genomewide association studies: History, rationale, and prospects for psychiatric disorders. Am J Psychiatry. 2009;166(5):540–556.
  • Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–753.
  • DeAngelis M, Ji F. Genetics of age-related macular degeneration. In: Albert & Jakobiec’s Principles & Practice of Ophthalmology, 3rd ed., Philadelphia, PA: Saunders, 2008,1881–1900.
  • Allikmets R, Seddon JM, Bernstein PS, et al. Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies. Hum. Genet. 1999;104(6):449–453.
  • Krämer F, White K, Pauleikhoff D, et al. Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration. Eur. J. Hum. Genet. 2000;8(4):286–292.
  • Lotery AJ, Munier FL, Fishman GA, et al. Allelic variation in the VMD2 gene in best disease and age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1291–1296.
  • Akimoto A, Akimoto M, Kuroiwa S, Kikuchi T, Yoshimura N. Lack of association of mutations of the bestrophin gene with age-related macular degeneration in non-familial Japanese patients. Graefes Arch. Clin. Exp. Ophthalmol. 2001;239(1):66–68.
  • Seddon JM, Afshari MA, Sharma S, et al. Assessment of mutations in the Best macular dystrophy (VMD2) gene in patients with adult-onset foveomacular vitelliform dystrophy, age-related maculopathy, and bull’s-eye maculopathy. Ophthalmology. 2001;108(11):2060–2067.
  • Kemp CM, Jacobson SG, Cideciyan AV, et al. RDS gene mutations causing retinitis pigmentosa or macular degeneration lead to the same abnormality in photoreceptor function. Invest. Ophthalmol. Vis. Sci. 1994;35(8):3154–3162.
  • Gorin MB, Jackson KE, Ferrell RE, et al. A peripherin/retinal degeneration slow mutation (Pro-210-Arg) associated with macular and peripheral retinal degeneration. Ophthalmology. 1995;102(2):246–255.
  • Stone EM, Lotery AJ, Munier FL, et al. A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy. Nat. Genet. 1999;22(2):199–202.
  • Guymer RH, McNeil R, Cain M, et al. Analysis of the Arg345Trp disease-associated allele of the EFEMP1 gene in individuals with early onset drusen or familial age-related macular degeneration. Clin. Experiment. Ophthalmol. 2002;30(6):419–423.
  • Narendran N, Guymer RH, Cain M, Baird PN. Analysis of the EFEMP1 gene in individuals and families with early onset drusen. Eye (Lond). 2005;19(1):11–15.
  • Allikmets R, Shroyer NF, Singh N, et al. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science. 1997;277(5333):1805–1807.
  • Allikmets R. Further evidence for an association of ABCR alleles with age-related macular degeneration. The International ABCR Screening Consortium. Am. J. Hum. Genet. 2000;67(2):487–491.
  • Stone EM, Webster AR, Vandenburgh K, et al. Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration. Nat. Genet. 1998;20(4):328–329.
  • De La Paz MA, Guy VK, Abou-Donia S, et al. Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration. Ophthalmology. 1999;106(8):1531–1536.
  • Souied EH, Ducroq D, Gerber S, et al. Age-related macular degeneration in grandparents of patients with Stargardt disease: Genetic study. Am. J. Ophthalmol. 1999;128(2):173–178.
  • Rivera A, White K, Stöhr H, et al. A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration. Am. J. Hum. Genet. 2000;67(4):800–813.
  • Guymer RH, Héon E, Lotery AJ, et al. Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated with age-related macular degeneration. Arch. Ophthalmol. 2001;119(5):745–751.
  • Webster AR, Héon E, Lotery AJ, et al. An analysis of allelic variation in the ABCA4 gene. Invest. Ophthalmol. Vis. Sci. 2001;42(6):1179–1189.
  • Bernstein PS, Leppert M, Singh N, et al. Genotype-phenotype analysis of ABCR variants in macular degeneration probands and siblings. Invest. Ophthalmol. Vis. Sci. 2002;43(2):466–473.
  • Schmidt S, Postel EA, Agarwal A, et al. Detailed analysis of allelic variation in the ABCA4 gene in age-related maculopathy. Invest. Ophthalmol. Vis. Sci. 2003;44(7):2868–2875.
  • Conley YP, Thalamuthu A, Jakobsdottir J, et al. Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy. Hum. Mol. Genet. 2005;14(14):1991–2002.
  • Ayyagari R, Zhang K, Hutchinson A, et al. Evaluation of the ELOVL4 gene in patients with age-related macular degeneration. Ophthalmic Genet. 2001;22(4):233–239.
  • Seitsonen S, Lemmelä S, Holopainen J, et al. Analysis of variants in the complement factor H, the elongation of very long chain fatty acids-like 4 and the hemicentin 1 genes of age-related macular degeneration in the Finnish population. Mol. Vis. 2006;12:796–801.
  • Seddon JM, Santangelo SL, Book K, Chong S, Cote J. A genomewide scan for age-related macular degeneration provides evidence for linkage to several chromosomal regions. Am. J. Hum. Genet. 2003;73(4):780–790.
  • Hosaka M, Südhof TC. Synapsin III, a novel synapsin with an unusual regulation by Ca2+. J. Biol. Chem. 1998;273(22):13371–13374.
  • Macgregor AM, Eberhart CG, Fraig M, Lu J, Halushka MK. Tissue inhibitor of matrix metalloproteinase-3 levels in the extracellular matrix of lung, kidney, and eye increase with age. J. Histochem. Cytochem. 2009;57(3):207–213.
  • Qi JH, Ebrahem Q, Moore N, et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): Inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat. Med. 2003;9(4):407–415.
  • De La Paz MA, Pericak-Vance MA, Lennon F, Haines JL, Seddon JM. Exclusion of TIMP3 as a candidate locus in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 1997;38(6):1060–1065.
  • Felbor U, Doepner D, Schneider U, Zrenner E, Weber BH. Evaluation of the gene encoding the tissue inhibitor of metalloproteinases-3 in various maculopathies. Invest. Ophthalmol. Vis. Sci. 1997;38(6):1054–1059.
  • Girirajan S, Eichler EE. Phenotypic variability and genetic susceptibility to genomic disorders. Hum. Mol. Genet. 2010;19(R2):R176–187.
  • Ku CS, Loy EY, Salim A, Pawitan Y, Chia KS. The discovery of human genetic variations and their use as disease markers: Past, present and future. J. Hum. Genet. 2010;55(7):403–415.
  • Frazer KA, Murray SS, Schork NJ, Topol EJ. Human genetic variation and its contribution to complex traits. Nat. Rev. Genet. 2009;10(4):241–251.
  • Hastings PJ, Lupski JR, Rosenberg SM, Ira G. Mechanisms of change in gene copy number. Nat. Rev. Genet. 2009;10(8):551–564.
  • Lupski JR. Genomic rearrangements and sporadic disease. Nat. Genet. 2007;39(7 Suppl):S43–47.
  • Weeks DE, Conley YP, Tsai HJ, et al. Age-related maculopathy: An expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions. Am. J. Ophthalmol. 2001;132(5):682–692.
  • Weeks DE, Conley YP, Tsai H, et al. Age-related maculopathy: A genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. Am. J. Hum. Genet. 2004;75(2):174–189.
  • Weeks DE, Conley YP, Mah TS, et al. A full genome scan for age-related maculopathy. Hum. Mol. Genet. 2000;9(9):1329–1349.
  • Schmidt S, Hauser MA, Scott WK, et al. Cigarette smoking strongly modifies the association of LOC387715 and age-related macular degeneration. Am. J. Hum. Genet. 2006;78(5):852–864.
  • Kanda A, Chen W, Othman M, et al. A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 2007;104(41):16227–16232.
  • Wang G, Spencer KL, Scott WK, et al. Analysis of the indel at the ARMS2 3’UTR in age-related macular degeneration. Hum. Genet. 2010;127(5):595–602.
  • Fritsche LG, Loenhardt T, Janssen A, et al. Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nat. Genet. 2008;40(7):892–896.
  • Wang G, Spencer KL, Court BL, et al. Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria. Invest. Ophthalmol. Vis. Sci. 2009;50(7):3084–3090.
  • Brantley MA, Fang AM, King JM, et al. Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab. Ophthalmology. 2007;114(12):2168–2173.
  • Shuler RK, Schmidt S, Gallins P, et al. Phenotype analysis of patients with the risk variant LOC387715 (A69S) in age-related macular degeneration. Am. J. Ophthalmol. 2008;145(2):303–307.
  • Andreoli MT, Morrison MA, Kim BJ, et al. Comprehensive analysis of complement factor H and LOC387715/ARMS2/HTRA1 variants with respect to phenotype in advanced age-related macular degeneration. Am. J. Ophthalmol. 2009;148(6):869–874.
  • Conley YP, Jakobsdottir J, Mah T, et al. CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses. Hum. Mol. Genet. 2006;15(21):3206–3218.
  • Ross RJ, Bojanowski CM, Wang JJ, et al. The LOC387715 polymorphism and age-related macular degeneration: Replication in three case-control samples. Invest. Ophthalmol. Vis. Sci. 2007;48(3):1128–1132.
  • Deangelis MM, Ji F, Adams S, et al. Alleles in the HtrA serine peptidase 1 gene alter the risk of neovascular age-related macular degeneration. Ophthalmology. 2008;115(7):1209–1215. e7.
  • Gotoh N, Nakanishi H, Hayashi H, et al. ARMS2 (LOC387715) variants in Japanese patients with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. Am. J. Ophthalmol. 2009;147(6):1037–1041, 1041.e1-2.
  • Gibbs D, Yang Z, Constantine R, et al. Further mapping of 10q26 supports strong association of HTRA1 polymorphisms with age-related macular degeneration. Vision Res. 2008;48(5):685–689.
  • Hadley D, Orlin A, Brown G, et al. Analysis of six genetic risk factors highly associated with AMD in the region surrounding ARMS2 and HTRA1 on chromosome 10, region q26. Invest. Ophthalmol. Vis. Sci. 2010;51(4):2191–2196.
  • Losonczy G, Fekete A, Vokó Z, et al. Analysis of complement factor H Y402H, LOC387715, HTRA1 polymorphisms and ApoE alleles with susceptibility to age-related macular degeneration in Hungarian patients. Acta Ophthalmol. 2009. Available at: http://www.ncbi.nlm.nih.gov.ezp-prod1.hul.harvard.edu/pubmed/19845562 [Accessed February 28, 2011].
  • Mori K, Horie-Inoue K, Gehlbach PL, et al. Phenotype and genotype characteristics of age-related macular degeneration in a Japanese population. Ophthalmology. 2010;117(5):928–938.
  • Yang Z, Tong Z, Chen Y, et al. Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration. PLoS Genet. 2010;6(2):e1000836.
  • Jiang H, Qu Y, Dang G, et al. Analyses of single nucleotide polymorphisms and haplotype linkage of LOC387715 and the HTRA1 gene in exudative age-related macular degeneration in a Chinese cohort. Retina 2009;29(7):974–979.
  • Bergeron-Sawitzke J, Gold B, Olsh A, et al. Multilocus analysis of age-related macular degeneration. Eur. J. Hum. Genet. 2009;17(9):1190–1199.
  • Farwick A, Dasch B, Weber BHF, et al. Variations in five genes and the severity of age-related macular degeneration: results from the Muenster aging and retina study. Eye (Lond). 2009;23(12):2238–2244.
  • An E, Sen S, Park SK, Gordish-Dressman H, Hathout Y. Identification of novel substrates for the serine protease HTRA1 in the human RPE secretome. Invest. Ophthalmol. Vis. Sci. 2010;51(7):3379–3386.
  • Zareparsi S, Branham KEH, Li M, et al. Strong association of the Y402H variant in complement factor H at 1q32 with susceptibility to age-related macular degeneration. Am. J. Hum. Genet. 2005;77(1):149–153.
  • Souied EH, Leveziel N, Richard F, et al. Y402H complement factor H polymorphism associated with exudative age-related macular degeneration in the French population. Mol. Vis. 2005;11:1135–1140.
  • Sepp T, Khan JC, Thurlby DA, et al. Complement factor H variant Y402H is a major risk determinant for geographic atrophy and choroidal neovascularization in smokers and nonsmokers. Invest. Ophthalmol. Vis. Sci. 2006;47(2):536–540.
  • Gotoh N, Yamada R, Hiratani H, et al. No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese. Hum. Genet. 2006;120(1):139–143.
  • Kardys I, Klaver CCW, Despriet DDG, et al. A common polymorphism in the complement factor H gene is associated with increased risk of myocardial infarction: The Rotterdam Study. J. Am. Coll. Cardiol. 2006;47(8):1568–1575.
  • Fremeaux-Bacchi V, Kemp EJ, Goodship JA, et al. The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: Evidence from two independent cohorts. J. Med. Genet. 2005;42(11):852–856.
  • Abrera-Abeleda MA, Nishimura C, Smith JLH, et al. Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease). J. Med. Genet. 2006;43(7):582–589.
  • Anderson DH, Radeke MJ, Gallo NB, et al. The pivotal role of the complement system in aging and age-related macular degeneration: Hypothesis re-visited. Prog Retin Eye Res. 2010;29(2):95–112.
  • Abarrategui-Garrido C, Martínez-Barricarte R, López-Trascasa M, de Có,rdoba SR, Sánchez-Corral P. Characterization of complement factor H-related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome. Blood. 2009;114(19):4261–4271.
  • Józsi M, Licht C, Strobel S, et al. Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood. 2008;111(3):1512–1514.
  • Moore I, Strain L, Pappworth I, et al. Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood. 2010;115(2):379–387.
  • Zipfel PF, Mache C, Müller D, et al. DEAP-HUS: Deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome. Pediatr. Nephrol. 2010;25(10):2009–2019.
  • Hageman GS, Hancox LS, Taiber AJ, et al. Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: Characterization, ethnic distribution and evolutionary implications. Ann. Med. 2006;38(8):592–604.
  • Spencer KL, Olson LM, Anderson BM, et al. C3 R102G polymorphism increases risk of age-related macular degeneration. Hum. Mol. Genet. 2008;17(12):1821–1824.
  • Pei X, Li X, Bao Y, et al. Association of c3 gene polymorphisms with neovascular age-related macular degeneration in a chinese population. Curr. Eye Res. 2009;34(8):615–622.
  • Arvilommi H. Capacity of complement c3 phenotypes to bind on to mononuclear cells in man. Nature. 1974;251(5477):740–741.
  • Park KH, Fridley BL, Ryu E, Tosakulwong N, Edwards AO. Complement component 3 (C3) haplotypes and risk of advanced age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(7):3386–3393.
  • McKay GJ, Dasari S, Patterson CC, Chakravarthy U, Silvestri G. Complement component 3: an assessment of association with AMD and analysis of gene-gene and gene-environment interactions in a Northern Irish cohort. Mol. Vis. 2010;16:194–199.
  • Cui L, Zhou H, Yu J, et al. Noncoding variant in the complement factor H gene and risk of exudative age-related macular degeneration in a Chinese population. Invest. Ophthalmol. Vis. Sci. 2010;51(2):1116–1120.
  • Farwick A, Wellmann J, Stoll M, Pauleikhoff D, Hense H. Susceptibility genes and progression in age-related maculopathy: A study of single eyes. Invest. Ophthalmol. Vis. Sci. 2010;51(2):731–736.
  • Donoso LA, Kim D, Frost A, Callahan A, Hageman G. The role of inflammation in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2006;51(2):137–152.
  • Francis PJ, Zhang H, Dewan A, Hoh J, Klein ML. Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on AMD in a Caucasian population. Mol. Vis. 2008;14:1395–1400.
  • Schaumberg DA, Hankinson SE, Guo Q, Rimm E, Hunter DJ. A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors. Arch. Ophthalmol. 2007;125(1):55–62.
  • Seddon JM, Reynolds R, Rosner B. Peripheral retinal drusen and reticular pigment: association with CFHY402H and CFHrs1410996 genotypes in family and twin studies. Invest. Ophthalmol. Vis. Sci. 2009;50(2):586–591.
  • Tuo J, Smith BC, Bojanowski CM, et al. The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration. FASEB J. 2004;18(11):1297–1299.
  • Matsumoto M, Seya T. TLR3: Interferon induction by double-stranded RNA including poly(I:C). Adv. Drug Deliv. Rev. 2008;60(7):805–812.
  • Yang Z, Stratton C, Francis PJ, et al. Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. N. Engl. J. Med. 2008;359(14):1456–1463.
  • Cho Y, Wang JJ, Chew EY, et al. Toll-like receptor polymorphisms and age-related macular degeneration: Replication in three case-control samples. Invest. Ophthalmol. Vis. Sci. 2009;50(12):5614–5618.
  • Edwards AO, Swaroop A, Seddon JM. Geographic atrophy in age-related macular degeneration and TLR3. N. Engl. J. Med. 2009;360(21):2254–2255; author reply 2255–2256.
  • Allikmets R, Bergen AA, Dean M, et al. Geographic atrophy in age-related macular degeneration and TLR3. N. Engl. J. Med. 2009;360(21):2252–2254; author reply 2255–2256.
  • Lewin AS. Geographic atrophy in age-related macular degeneration and TLR3. N. Engl. J. Med. 2009;360(21):2251; author reply 2255–2256.
  • Kiechl S, Lorenz E, Reindl M, et al. Toll-like receptor 4 polymorphisms and atherogenesis. N. Engl. J. Med. 2002;347(3):185–192.
  • Boekholdt SM, Agema WRP, Peters RJG, et al. Variants of toll-like receptor 4 modify the efficacy of statin therapy and the risk of cardiovascular events. Circulation. 2003;107(19):2416–2421.
  • Zareparsi S, Buraczynska M, Branham KEH, et al. Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration. Hum. Mol. Genet. 2005;14(11):1449–1455.
  • Despriet DDG, Bergen AAB, Merriam JE, et al. Comprehensive analysis of the candidate genes CCL2, CCR2, and TLR4 in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(1):364–371.
  • Edwards AO, Chen D, Fridley BL, et al. Toll-like receptor polymorphisms and age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(4):1652–1659.
  • Saunders AM. Apolipoprotein E and Alzheimer disease: An update on genetic and functional analyses. J. Neuropathol. Exp. Neurol. 2000;59(9):751–758.
  • Klaver CC, Kliffen M, van Duijn CM, et al. Genetic association of apolipoprotein E with age-related macular degeneration. Am. J. Hum. Genet. 1998;63(1):200–206.
  • Souied EH, Benlian P, Amouyel P, et al. The epsilon4 allele of the apolipoprotein E gene as a potential protective factor for exudative age-related macular degeneration. Am. J. Ophthalmol. 1998;125(3):353–359.
  • Schmidt S, Saunders AM, De La Paz MA, et al. Association of the apolipoprotein E gene with age-related macular degeneration: Possible effect modification by family history, age, and gender. Mol. Vis. 2000;6:287–293.
  • Simonelli F, Margaglione M, Testa F, et al. Apolipoprotein E polymorphisms in age-related macular degeneration in an Italian population. Ophthalmic Res. 2001;33(6):325–328.
  • Schmidt S, Klaver C, Saunders A, et al. A pooled case-control study of the apolipoprotein E (APOE) gene in age-related maculopathy. Ophthalmic Genet. 2002;23(4):209–223.
  • Zareparsi S, Reddick AC, Branham KEH, et al. Association of apolipoprotein E alleles with susceptibility to age-related macular degeneration in a large cohort from a single center. Invest. Ophthalmol. Vis. Sci. 2004;45(5):1306–1310.
  • Baird PN, Guida E, Chu DT, Vu HTV, Guymer RH. The epsilon2 and epsilon4 alleles of the apolipoprotein gene are associated with age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2004;45(5):1311–1315.
  • Pang CP, Baum L, Chan WM, et al. The apolipoprotein E epsilon4 allele is unlikely to be a major risk factor of age-related macular degeneration in Chinese. Ophthalmologica. 2000;214(4):289–291.
  • Schultz DW, Klein ML, Humpert A, et al. Lack of an association of apolipoprotein E gene polymorphisms with familial age-related macular degeneration. Arch. Ophthalmol. 2003;121(5):679–683.
  • Gotoh N, Kuroiwa S, Kikuchi T, et al. Apolipoprotein E polymorphisms in Japanese patients with polypoidal choroidal vasculopathy and exudative age-related macular degeneration. Am. J. Ophthalmol. 2004;138(4):567–573.
  • Schmidt S, Haines JL, Postel EA, et al. Joint effects of smoking history and APOE genotypes in age-related macular degeneration. Mol. Vis. 2005;11:941–949.
  • Ikeda T, Obayashi H, Hasegawa G, et al. Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as possible risk factors for exudative age-related macular degeneration. Am. J. Ophthalmol. 2001;132(2):191–195.
  • Hara K, Shiga A, Fukutake T, et al. Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N. Engl. J. Med. 2009;360(17):1729–1739.
  • Baird PN, Chu D, Guida E, Vu HTV, Guymer R. Association of the M55L and Q192R paraoxonase gene polymorphisms with age-related macular degeneration. Am. J. Ophthalmol. 2004;138(4):665–666.
  • Esfandiary H, Chakravarthy U, Patterson C, Young I, Hughes AE. Association study of detoxification genes in age related macular degeneration. Br J Ophthalmol. 2005;89(4):470–474.
  • Haines JL, Schnetz-Boutaud N, Schmidt S, et al. Functional candidate genes in age-related macular degeneration: Significant association with VEGF, VLDLR, and LRP6. Invest. Ophthalmol. Vis. Sci. 2006;47(1):329–335.
  • Frykman PK, Brown MS, Yamamoto T, Goldstein JL, Herz J. Normal plasma lipoproteins and fertility in gene-targeted mice homozygous for a disruption in the gene encoding very low density lipoprotein receptor. Proc. Natl. Acad. Sci. U.S.A. 1995;92(18):8453–8457.
  • Heckenlively JR, Hawes NL, Friedlander M, et al. Mouse model of subretinal neovascularization with choroidal anastomosis. Retina 2003;23(4):518–522.
  • Hu W, Jiang A, Liang J, et al. Expression of VLDLR in the retina and evolution of subretinal neovascularization in the knockout mouse model’s retinal angiomatous proliferation. Invest. Ophthalmol. Vis. Sci. 2008;49(1):407–415.
  • Tuo J, Ning B, Bojanowski CM, et al. Synergic effect of polymorphisms in ERCC6 5’ flanking region and complement factor H on age-related macular degeneration predisposition. Proc. Natl. Acad. Sci. U.S.A. 2006;103(24):9256–9261.
  • Schultz DW, Klein ML, Humpert AJ, et al. Analysis of the ARMD1 locus: Evidence that a mutation in HEMICENTIN-1 is associated with age-related macular degeneration in a large family. Hum. Mol. Genet. 2003;12(24):3315–3323.
  • Hayashi M, Merriam JE, Klaver CCW, et al. Evaluation of the ARMD1 locus on 1q25–31 in patients with age-related maculopathy: Genetic variation in laminin genes and in exon 104 of HEMICENTIN-1. Ophthalmic Genet. 2004;25(2):111–119.
  • Stone EM, Braun TA, Russell SR, et al. Missense variations in the fibulin 5 gene and age-related macular degeneration. N. Engl. J. Med. 2004;351(4):346–353.
  • Lotery AJ, Baas D, Ridley C, et al. Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa. Hum. Mutat. 2006;27(6):568–574.
  • Kimura K, Isashiki Y, Sonoda S, Kakiuchi-Matsumoto T, Ohba N. Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration. Am. J. Ophthalmol. 2000;130(6):769–773.
  • Gotoh N, Yamada R, Matsuda F, Yoshimura N, Iida T. Manganese superoxide dismutase gene (SOD2) polymorphism and exudative age-related macular degeneration in the Japanese population. Am. J. Ophthalmol. 2008;146(1):146; author reply 146–147.
  • Kondo N, Bessho H, Honda S, Negi A. SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Mol. Vis. 2009;15:1819–1826.
  • Zurdel J, Finckh U, Menzer G, Nitsch RM, Richard G. CST3 genotype associated with exudative age related macular degeneration. Br J Ophthalmol. 2002;86(2):214–219.
  • Hamdi HK, Reznik J, Castellon R, et al. Alu DNA polymorphism in ACE gene is protective for age-related macular degeneration. Biochem. Biophys. Res. Commun. 2002;295(3):668–672.
  • Churchill AJ, Carter JG, Lovell HC, et al. VEGF polymorphisms are associated with neovascular age-related macular degeneration. Hum. Mol. Genet. 2006;15(19):2955–2961.
  • Janik-Papis K, Zaras M, Krzyzanowska A, et al. Association between vascular endothelial growth factor gene polymorphisms and age-related macular degeneration in a Polish population. Exp. Mol. Pathol. 2009;87(3):234–238.
  • Francis PJ, Hamon SC, Ott J, Weleber RG, Klein ML. Polymorphisms in C2, CFB and C3 are associated with progression to advanced age related macular degeneration associated with visual loss. J. Med. Genet. 2009;46(5):300–307.
  • Fang AM, Lee AY, Kulkarni M, Osborn MP, Brantley MA. Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration. Mol. Vis. 2009;15:2710–2719.
  • Boekhoorn SS, Isaacs A, Uitterlinden AG, et al. Polymorphisms in the vascular endothelial growth factor gene and risk of age-related macular degeneration: The Rotterdam Study. Ophthalmology. 2008;115(11):1899–1903.
  • Besnard S, Silvestre JS, Duriez M, et al. Increased ischemia-induced angiogenesis in the staggerer mouse, a mutant of the nuclear receptor Roralpha. Circ. Res. 2001;89(12):1209–1215.
  • Hageman GS, Luthert PJ, Victor Chong NH, et al. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res. 2001;20(6):705–732.
  • Anderson DH, Mullins RF, Hageman GS, Johnson LV. A role for local inflammation in the formation of drusen in the aging eye. Am. J. Ophthalmol. 2002;134(3):411–431.
  • Klein R, Klein BEK, Tomany SC, Danforth LG, Cruickshanks KJ. Relation of statin use to the 5-year incidence and progression of age-related maculopathy. Arch. Ophthalmol. 2003;121(8):1151–1155.
  • Boukhtouche F, Mariani J, Tedgui A. The “CholesteROR” protective pathway in the vascular system. Arterioscler. Thromb. Vasc. Biol. 2004;24(4):637–643.
  • Johnson EJ. Obesity, lutein metabolism, and age-related macular degeneration: A web of connections. Nutr. Rev. 2005;63(1):9–15.
  • Zhu Y, McAvoy S, Kuhn R, Smith DI. RORA, a large common fragile site gene, is involved in cellular stress response. Oncogene. 2006;25(20):2901–2908.
  • Lau P, Fitzsimmons RL, Raichur S, et al. The orphan nuclear receptor, RORalpha, regulates gene expression that controls lipid metabolism: Staggerer (SG/SG) mice are resistant to diet-induced obesity. J. Biol. Chem. 2008;283(26):18411–18421.
  • Schaumberg DA, Chasman D, Morrison MA, et al. Prospective study of common variants in the retinoic acid receptor-related orphan receptor α gene and risk of neovascular age-related macular degeneration. Arch. Ophthalmol. 2010;128(11):1462–1471.
  • Scholl HPN, Charbel Issa P, Walier M, et al. Systemic complement activation in age-related macular degeneration. PLoS ONE. 2008;3(7):e2593.
  • Hollams EM, Giles KM, Thomson AM, Leedman PJ. MRNA stability and the control of gene expression: Implications for human disease. Neurochem. Res. 2002;27(10):957–980.
  • Maddox DM, Vessey KA, Yarbrough GL, et al. Allelic variance between GRM6 mutants, Grm6nob3 and Grm6nob4 results in differences in retinal ganglion cell visual responses. J. Physiol. (Lond.). 2008;586(Pt 18):4409–4424.
  • Margulies EH, Birney E. Approaches to comparative sequence analysis: Towards a functional view of vertebrate genomes. Nat. Rev. Genet. 2008;9(4):303–313.
  • Reynolds R, Rosner B, Seddon JM. Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration. Ophthalmology. 2010;117(10):1989–1995.
  • Gu J, Pauer GJT, Yue X, et al. Proteomic and genomic biomarkers for age-related macular degeneration. Adv Exp Med Biol. 2010;664:411–417.
  • Robman L, Baird PN, Dimitrov PN, Richardson AJ, Guymer RH. C-reactive protein levels and complement factor H polymorphism interaction in age-related macular degeneration and its progression. Ophthalmology. 2010;117(10):1982–1988.
  • Gu J, Pauer GJT, Yue X, et al. Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers. Mol. Cell Proteomics. 2009;8(6):1338–1349.
  • Ni J, Yuan X, Gu J, et al. Plasma protein pentosidine and carboxymethyllysine, biomarkers for age-related macular degeneration. Mol. Cell Proteomics. 2009;8(8):1921–1933.
  • Lu L, Gu X, Hong L, et al. Synthesis and structural characterization of carboxyethylpyrrole-modified proteins: Mediators of age-related macular degeneration. Bioorg. Med. Chem. 2009;17(21):7548–7561.
  • Klein R, Knudtson MD, Lee KE, Klein BEK. Serum cystatin C level, kidney disease markers, and incidence of age-related macular degeneration: The Beaver Dam Eye Study. Arch. Ophthalmol. 2009;127(2):193–199.
  • Boekhoorn SS, Vingerling JR, Witteman JCM, Hofman A, de Jong PTVM. C-reactive protein level and risk of aging macula disorder: The Rotterdam Study. Arch. Ophthalmol. 2007;125(10):1396–1401.
  • Wang JJ, Ross RJ, Tuo J, et al. The LOC387715 polymorphism, inflammatory markers, smoking, and age-related macular degeneration. A population-based case-control study. Ophthalmology. 2008;115(4):693–699.
  • Vine AK, Stader J, Branham K, Musch DC, Swaroop A. Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration. Ophthalmology. 2005;112(12):2076–2080.
  • Richer S, Rudy D, Statkute L, Karofty K, Frankowski J. Serum iron, transferrin saturation, ferritin, and dietary data in age-related macular degeneration. Am J Ther. 2002;9(1):25–28.
  • Smith W, Mitchell P, Rochester C. Serum beta carotene, alpha tocopherol, and age-related maculopathy: The Blue Mountains Eye Study. Am. J. Ophthalmol. 1997;124(6):838–840.
  • Crabb JW, Miyagi M, Gu X, et al. Drusen proteome analysis: An approach to the etiology of age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 2002;99(23):14682–14687.
  • Ethen CM, Reilly C, Feng X, Olsen TW, Ferrington DA. The proteome of central and peripheral retina with progression of age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2006;47(6):2280–2290.
  • Nordgaard CL, Karunadharma PP, Feng X, Olsen TW, Ferrington DA. Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(7):2848–2855.
  • Gu J, Pauer GJ, Yue X, Narendra U, Sturgill GM, Bena J, Gu X, Peachey NS, Salomon RG, Hagstrom SA, Crabb JW. The Clinical Genomic and Proteomic AMD Study Group. Proteomic and genomic biomarkers for age-related macular degeneration. Adv Exp Med Biol. 2010;664:411–417.
  • Jones MM, Manwaring N, Wang JJ, Rochtchina E, Mitchell P, Sue CM. Mitochondrial DNA haplogroups and age-related maculopathy. Arch Ophthalmol. 2007 Sep;125(9):1235–40.
  • SanGiovanni JP, Arking DE, Iyengar SK, Elashoff M, Clemons TE, Reed GF, Henning AK, Sivakumaran TA, Xu X, DeWan A, Agrón E, Rochtchina E, Sue CM, Wang JJ, Mitchell P, Hoh J, Francis PJ, Klein ML, Chew EY, Chakravarti A. Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration.PLoS One. 2009;4(5):e5508. Epub 2009 May 12.
  • Hamsten A, Eriksson P. Identifying the susceptibility genes for coronary artery disease: from hyperbole through doubt to cautious optimism. J. Intern. Med. 2008;263(5):538–552.
  • Seddon JM, Reynolds R, Maller J, Fagerness JA, Daly MJ, Rosner B. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest Ophthalmol Vis Sci. 2009 May;50(5):2044–53.

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