Review of Genetics in Age Related Macular Degeneration

Age-related macular degeneration (AMD) is a degenerative disease of the retina and the leading cause of blindness in industrialized countries. AMD is a complex disease caused by the combination of genetic predisposition and environmental factors. The prevalence of AMD increases with age. The adverse effect of smoking is well established. Genetic predisposition has been demonstrated by familial aggregation studies and twin studies. Using genome linkage scan and association studies, multiple potentially causative genes have been identified. The chromosomes most commonly implicated are 1q25-31 and 10q26. In particular, variants in the gene for the complement factor H (CFH) and the genes PLEKHA1/LOC387715/HTRA1, Factor B (BF) and complement component 2 (C2) have been implicated as major risk or protective factors for the development of AMD. There have been some advances in the treatment of this condition; however, a complete cure remains remote but hopeful. Understanding the causative environmental and genetic interactions will facilitate the development of future preventive methods and treatments.

[1]  A E Fletcher,et al.  28 000 Cases of age related macular degeneration causing visual loss in people aged 75 years and above in the United Kingdom may be attributable to smoking , 2005, British Journal of Ophthalmology.

[2]  Y. Nose,et al.  The 5-year incidence and risk factors for age-related maculopathy in a general Japanese population: the Hisayama study. , 2005, Investigative ophthalmology & visual science.

[3]  J. J. Wang,et al.  Risk factors for age-related maculopathy: the Visual Impairment Project. , 2001, Archives of ophthalmology.

[4]  G. Tikellis,et al.  Apolipoprotein (APOE) gene is associated with progression of age‐related macular degeneration (AMD) , 2006, Human mutation.

[5]  A. Moore,et al.  Genetic susceptibility to age related macular degeneration , 2000, Journal of medical genetics.

[6]  B. Munoz,et al.  Exposure to sunlight and other risk factors for age-related macular degeneration. , 1989, Archives of ophthalmology.

[7]  B. Ning,et al.  An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation , 2006, Environmental and molecular mutagenesis.

[8]  Johanna M Seddon,et al.  The genetics of age-related macular degeneration: a review of progress to date. , 2006, Survey of ophthalmology.

[9]  Ching-Yu Cheng,et al.  Association of the Y402H polymorphism in complement factor H gene and neovascular age-related macular degeneration in Chinese patients. , 2006, Investigative ophthalmology & visual science.

[10]  M. Klein,et al.  Heredity and age-related macular degeneration. Observations in monozygotic twins. , 1994, Archives of ophthalmology.

[11]  M. Klein,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. , 2003, Human molecular genetics.

[12]  W. Green,et al.  Detection of CX3CR1 single nucleotide polymorphism and expression on archived eyes with age-related macular degeneration. , 2005, Histology and histopathology.

[13]  J. Mares Potential value of antioxidant-rich foods in slowing age-related macular degeneration. , 2006, Archives of ophthalmology.

[14]  R Hiller,et al.  Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. , 1994, JAMA.

[15]  J. Hoh,et al.  Systematic review and meta-analysis of the association between complement factor H Y402H polymorphisms and age-related macular degeneration. , 2006, Human molecular genetics.

[16]  B. Rosner,et al.  Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: the US Twin Study of Age-Related Macular Degeneration. , 2006, Archives of ophthalmology.

[17]  F. Testa,et al.  Polymorphism p.402Y>H in the complement factor H protein is a risk factor for age related macular degeneration in an Italian population , 2006, British Journal of Ophthalmology.

[18]  D. Friedman,et al.  Racial differences in the prevalence of age-related macular degeneration: the Baltimore Eye Survey. , 1999, Ophthalmology.

[19]  Liang Xu,et al.  Associated factors for age related maculopathy in the adult population in China: the Beijing eye study , 2006, British Journal of Ophthalmology.

[20]  L. Marmorstein Association of EFEMP1 with malattia leventinese and age-related macular degeneration: a mini-review , 2004, Ophthalmic genetics.

[21]  R. Klein,et al.  The prevalence of age-related maculopathy by geographic region and ethnicity. The Colorado-Wisconsin Study of Age-Related Maculopathy. , 1997, Archives of ophthalmology.

[22]  Shigeo Yoshida,et al.  Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease. , 2004, American journal of human genetics.

[23]  P. Mitchell,et al.  Smoking and age-related macular degeneration: a review of association , 2005, Eye.

[24]  J. Lupski,et al.  A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Starqardt macular dystrophy , 1997, Nature Genetics.

[25]  J. J. Wang,et al.  Prevalence of age-related maculopathy in Australia. The Blue Mountains Eye Study. , 1995, Ophthalmology.

[26]  P T de Jong,et al.  An international classification and grading system for age-related maculopathy and age-related macular degeneration , 1995 .

[27]  J. J. Wang,et al.  Plasma fibrinogen levels, other cardiovascular risk factors, and age-related maculopathy: the Blue Mountains Eye Study. , 1998, Archives of ophthalmology.

[28]  J. J. Wang,et al.  The prevalence of age-related maculopathy: the visual impairment project. , 2000, Ophthalmology.

[29]  C. Osmond,et al.  Association of HLA class I and class II polymorphisms with age-related macular degeneration. , 2005, Investigative ophthalmology & visual science.

[30]  N. Orr,et al.  A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration , 2006, Nature Genetics.

[31]  B. Rosner,et al.  Association of CFH Y402H and LOC387715 A69S with progression of age-related macular degeneration. , 2007, JAMA.

[32]  T. Matise,et al.  Age-related macular degeneration--a genome scan in extended families. , 2003, American journal of human genetics.

[33]  A. D. de Lorimier Alcohol, wine, and health. , 2000, American journal of surgery.

[34]  T. Peto,et al.  5-year incidence of age-related maculopathy in the Reykjavik Eye Study. , 2003, Ophthalmology.

[35]  Lawrence A. Yannuzzi,et al.  Dietary Carotenoids, Vitamins A, C, and E, and Advanced Age-Related Macular Degeneration , 1994 .

[36]  U. Brunk,et al.  Lipofuscin formation in cultured retinal pigment epithelial cells exposed to photoreceptor outer segment material under different oxygen concentrations , 1996, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[37]  A. Hutchinson,et al.  The ABCR gene in recessive and dominant Stargardt diseases: a genetic pathway in macular degeneration. , 1999, Genomics.

[38]  A. Hofman,et al.  REVIEW: Epidemiology of age-related maculopathy: a review , 2003, European Journal of Epidemiology.

[39]  E. Stefánsson,et al.  Age related macular degeneration in monozygotic twins and their spouses in Iceland. , 1999, Acta ophthalmologica Scandinavica.

[40]  N. Yoshimura,et al.  ATP binding cassette transporter retina genotypes and age related macular degeneration: an analysis on exudative non-familial Japanese patients , 1999, The British journal of ophthalmology.

[41]  B S Hawkins,et al.  Epidemiology of age-related macular degeneration. , 1999, Molecular vision.

[42]  Lezheng Wu,et al.  Study of aging macular degeneration in China. , 1987, Japanese journal of ophthalmology.

[43]  R. Allikmets,et al.  Further evidence for an association of ABCR alleles with age-related macular degeneration. The International ABCR Screening Consortium. , 2000, American journal of human genetics.

[44]  T. Triche,et al.  Population-based study of early age-related macular degeneration: role of the complement factor H Y402H polymorphism in bilateral but not unilateral disease. , 2007, Ophthalmology.

[45]  A Hofman,et al.  Risk factors for age-related macular degeneration: Pooled findings from three continents. , 2001, Ophthalmology.

[46]  J. Haines,et al.  Cigarette smoking strongly modifies the association of LOC387715 and age-related macular degeneration. , 2006, American journal of human genetics.

[47]  J. Lupski,et al.  Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration. , 2001, Human molecular genetics.

[48]  J. Gilbert,et al.  Joint effects of smoking history and APOE genotypes in age-related macular degeneration. , 2005, Molecular vision.

[49]  B. Rosner,et al.  Progression of age-related macular degeneration: association with dietary fat, transunsaturated fat, nuts, and fish intake. , 2003, Archives of ophthalmology.

[50]  A. Tamakoshi,et al.  Report on the nationwide epidemiological survey of exudative age-related macular degeneration in Japan , 2004, International Ophthalmology.

[51]  M. Killingsworth,et al.  Macrophages related to Bruch's membrane in age-related macular degeneration , 1990, Eye.

[52]  Yun Li,et al.  CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration , 2006, Nature Genetics.

[53]  J. Lupski,et al.  Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. , 1997, Science.

[54]  S. Nilsson,et al.  Lipofuscin-formation in retinal pigment epithelial cells is reduced by antioxidants. , 2001, Free radical biology & medicine.

[55]  J. Manson,et al.  A prospective study of alcohol consumption and the risk of age-related macular degeneration. , 1999, Annals of epidemiology.

[56]  C. Klaver,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 , 2004, Ophthalmic genetics.

[57]  U. Brunk,et al.  Aging of cultured retinal pigment epithelial cells: oxidative reactions, lipofuscin formation and blue light damage , 2004, Documenta Ophthalmologica.

[58]  R. Elston,et al.  Oral zinc in macular degeneration. , 1988, Archives of ophthalmology.

[59]  B. Lorenz,et al.  A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration. , 2000, American journal of human genetics.

[60]  J. Provis,et al.  Modulation of major histocompatibility complex class II expression in retinas with age-related macular degeneration. , 1997, Investigative ophthalmology & visual science.

[61]  R. T. Smith,et al.  A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[62]  J. Ott,et al.  Complement Factor H Polymorphism in Age-Related Macular Degeneration , 2005, Science.

[63]  Benita J. O’Colmain,et al.  Prevalence of age-related macular degeneration in the United States. , 2004, Archives of ophthalmology.

[64]  Kei Shinoda,et al.  Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[65]  E. Rimm,et al.  Prospective study of dietary fat and the risk of age-related macular degeneration. , 2001, The American journal of clinical nutrition.

[66]  A. Bird,et al.  The prevalence of age-related maculopathy (ARM) in an urban Norwegian population: the Oslo Macular study. , 2003, Acta ophthalmologica Scandinavica.

[67]  A. Edwards,et al.  Complement Factor H Polymorphism and Age-Related Macular Degeneration , 2005, Science.

[68]  S. Russell,et al.  Vitronectin is a constituent of ocular drusen and the vitronectin gene is expressed in human retinal pigmented epithelial cells , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[69]  Johannes R. Vingerling,et al.  The prevalence of age-related maculopathy in the Rotterdam Study. , 1995, Ophthalmology.

[70]  B. Rosner,et al.  Progression of age-related macular degeneration: association with body mass index, waist circumference, and waist-hip ratio. , 2003, Archives of ophthalmology.

[71]  A. Capone,et al.  Symptomatic choroidal neovascularization in blacks. , 1994, Archives of ophthalmology.

[72]  D F Schorderet,et al.  Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated with age-related macular degeneration. , 2001, Archives of ophthalmology.

[73]  Ammarin Thakkinstian,et al.  Systematic review and meta-analysis of the association between complementary factor H Y402H polymorphisms and age-related macular degeneration , 2006 .

[74]  M. Smith-Wheelock,et al.  Association of apolipoprotein E alleles with susceptibility to age-related macular degeneration in a large cohort from a single center. , 2004, Investigative ophthalmology & visual science.

[75]  B. Rosner,et al.  CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration. , 2006, Human heredity.

[76]  G. Silvestri,et al.  Is genetic predisposition an important risk factor in age-related macular degeneration? , 1994, Eye.

[77]  Suzen M. Moeller,et al.  Ethnic Differences in Diet and Age-Related Maculopathies , 2003, International ophthalmology clinics.

[78]  E. Rimm,et al.  A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors. , 2007, Archives of ophthalmology.

[79]  T. Peto,et al.  The prevalence of age-related maculopathy in iceland: Reykjavik eye study. , 2002, Archives of ophthalmology.

[80]  J. J. Wang,et al.  Iris color, skin sun sensitivity, and age-related maculopathy. The Blue Mountains Eye Study. , 1998, Ophthalmology.

[81]  R. Guymer,et al.  Body Mass Index Modifiable Risk Factors for Age-related Macular Degeneration , 2006 .

[82]  Richard P. O. Jones,et al.  Reduced secretion of fibulin 5 in age‐related macular degeneration and cutis laxa , 2006, Human mutation.

[83]  M. Gillies,et al.  Immunological and Aetiological Aspects of Macular Degeneration , 2001, Progress in Retinal and Eye Research.

[84]  R. Klein,et al.  Smoking, alcohol intake, estrogen use, and age-related macular degeneration in Latinos: the Los Angeles Latino Eye Study. , 2006, American journal of ophthalmology.

[85]  D. Clayton,et al.  Complement factor H variant Y402H is a major risk determinant for geographic atrophy and choroidal neovascularization in smokers and nonsmokers. , 2006, Investigative ophthalmology & visual science.

[86]  E. Stone,et al.  Fibulin-5 distribution in human eyes: relevance to age-related macular degeneration. , 2007, Experimental eye research.

[87]  CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses. , 2007, Human molecular genetics.

[88]  W. Willett,et al.  Dietary fat and risk for advanced age-related macular degeneration. , 2001, Archives of ophthalmology.

[89]  P. Sieving,et al.  Evaluation of the ELOVL4 gene in patients with age-related macular degeneration , 2001, Ophthalmic genetics.

[90]  D. Weeks,et al.  Susceptibility genes for age-related maculopathy on chromosome 10q26. , 2005, American journal of human genetics.

[91]  N. Camp,et al.  A Variant of the HTRA1 Gene Increases Susceptibility to Age-Related Macular Degeneration , 2006, Science.

[92]  Robert F Mullins,et al.  A role for local inflammation in the formation of drusen in the aging eye. , 2002, American journal of ophthalmology.

[93]  Jurg Ott,et al.  Strong association of the Y402H variant in complement factor H at 1q32 with susceptibility to age-related macular degeneration. , 2005, American journal of human genetics.

[94]  Robert F. Mullins,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 , 2001, Progress in Retinal and Eye Research.

[95]  A. Munnich,et al.  ABCR gene analysis in familial exudative age-related macular degeneration. , 2000, Investigative ophthalmology & visual science.

[96]  N. Rifai,et al.  Association between C-reactive protein and age-related macular degeneration. , 2004, JAMA.

[97]  D. Weeks,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. , 2005, Human molecular genetics.

[98]  H. Hamdi,et al.  Age-related macular degeneration: a new viewpoint. , 2003, Frontiers in bioscience : a journal and virtual library.

[99]  R. Klein,et al.  Sunlight and the 5-year incidence of early age-related maculopathy: the beaver dam eye study. , 2001, Archives of ophthalmology.

[100]  M. Shimura,et al.  Molecular genetic analysis of ABCR gene in Japanese dry form age-related macular degeneration. , 2000, Japanese journal of ophthalmology.

[101]  J. Gilbert,et al.  Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration , 2005, Science.

[102]  Johanna M Seddon,et al.  Risk factors for the incidence of Advanced Age-Related Macular Degeneration in the Age-Related Eye Disease Study (AREDS) AREDS report no. 19. , 2003, Ophthalmology.

[103]  J. Haines,et al.  Age-related maculopathy: a genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. , 2004, American journal of human genetics.

[104]  Marco A Zarbin,et al.  Current concepts in the pathogenesis of age-related macular degeneration. , 2004, Archives of ophthalmology.

[105]  Susan Sanders DeBlack Cigarette smoking as a risk factor for cataract and age-related macular degeneration: a review of the literature. , 2003, Optometry.

[106]  Lars G Fritsche,et al.  Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. , 2005, Human molecular genetics.

[107]  J. Lupski,et al.  Corrigendum: A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy , 1997, Nature Genetics.

[108]  Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-Related Eye Disease Study Report Number 3. , 2000, Ophthalmology.

[109]  R. Klein,et al.  Risk of incident age-related eye diseases in people with an affected sibling : The Beaver Dam Eye Study. , 2001, American journal of epidemiology.

[110]  T. Matise,et al.  Age-related macular degeneration. Clinical features in a large family and linkage to chromosome 1q. , 1998, Archives of ophthalmology.

[111]  Chi Pui Pang,et al.  HTRA1 promoter polymorphism in wet age-related macular degeneration. , 2007, Science.

[112]  F L Ferris,et al.  Senile macular degeneration: a case-control study. , 1983, American journal of epidemiology.

[113]  W. Willett,et al.  A prospective study of cigarette smoking and age-related macular degeneration in women. , 1996, Journal of the American Medical Association (JAMA).

[114]  P. Mitchell,et al.  Five‐year incidence of age‐related maculopathyin relation to iris, skin or hair colour, and skin sun sensitivity:the Blue Mountains Eye Study , 2003, Clinical & experimental ophthalmology.

[115]  A Hofman,et al.  Genetic risk of age-related maculopathy. Population-based familial aggregation study. , 1998, Archives of ophthalmology.

[116]  M. C. Leske,et al.  Prevalence of open-angle glaucoma among adults in the United States. , 2004, Archives of ophthalmology.

[117]  V. Fischetti,et al.  M Protein of the Group A StreptococcusBinds to the Seventh Short Consensus Repeat of Human Complement Factor H , 1998, Infection and Immunity.

[118]  S. Russell,et al.  Drusen associated with aging and age‐related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[119]  I. Deary,et al.  Complement C3 variant and the risk of age-related macular degeneration. , 2007, The New England journal of medicine.

[120]  Ronald Klein,et al.  The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam eye study. , 2003, Ophthalmology.

[121]  J. Ott,et al.  The LOC387715 Gene, Smoking, Body Mass Index, Environmental Associations with Advanced Age-Related Macular Degeneration , 2007, Human Heredity.

[122]  R. Klein,et al.  Ten-year incidence and progression of age-related maculopathy: The Beaver Dam eye study. , 2002, Ophthalmology.

[123]  P. Zipfel,et al.  Identification of the second heparin-binding domain in human complement factor H. , 1998, Journal of immunology.

[124]  N. Yoshimura,et al.  Apolipoprotein E polymorphisms in Japanese patients with polypoidal choroidal vasculopathy and exudative age-related macular degeneration. , 2004, American journal of ophthalmology.

[125]  Y. Nose,et al.  Risk factors for age related maculopathy in a Japanese population: the Hisayama study , 2003, The British journal of ophthalmology.

[126]  Jennifer I. Lim,et al.  A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. , 2001, Archives of ophthalmology.

[127]  Santa Jeremy Ono,et al.  Circulating anti‐retinal antibodies as immune markers in age‐related macular degeneration , 2005, Immunology.

[128]  W. Willett,et al.  Prospective study of intake of fruits, vegetables, vitamins, and carotenoids and risk of age-related maculopathy. , 2004, Archives of ophthalmology.

[129]  A. D. Lorimier,et al.  Alcohol, wine, and health , 2000 .

[130]  A. Hofman,et al.  Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration. , 2006, JAMA.

[131]  G. Abecasis,et al.  Meta-analysis of genome scans of age-related macular degeneration. , 2005, Human molecular genetics.

[132]  C. Delcourt,et al.  Light exposure and the risk of age-related macular degeneration: the Pathologies Oculaires Liées à l'Age (POLA) study. , 2001, Archives of ophthalmology.

[133]  V. McIlvain,et al.  Reprogramming of Eye Progenitor Cells by Ectopic Expression of Neural Retinal Leucine Zipper Nrl Orthologs , 2006 .

[134]  E. Chew,et al.  The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age‐related macular degeneration , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[135]  Johanna M Seddon,et al.  The US twin study of age-related macular degeneration: relative roles of genetic and environmental influences. , 2005, Archives of ophthalmology.

[136]  S. Ranganathan,et al.  A common site within factor H SCR 7 responsible for binding heparin, C-reactive protein and streptococcal M protein. , 2000, European journal of immunology.

[137]  S. Sivaprasad,et al.  The complement system and age-related macular degeneration , 2006, Eye.

[138]  R. Frank,et al.  Race, iris color, and age-related macular degeneration. , 2000, Transactions of the American Ophthalmological Society.

[139]  Ivana K. Kim,et al.  Cigarette smoking, CFH, APOE, ELOVL4, and risk of neovascular age-related macular degeneration. , 2007, Archives of ophthalmology.

[140]  D. Lublin,et al.  Identification of a heparin binding domain in the seventh short consensus repeat of complement factor H. , 1996, Journal of immunology.

[141]  V. Sheffield,et al.  Missense variations in the fibulin 5 gene and age-related macular degeneration. , 2004, The New England journal of medicine.

[142]  R. T. Smith,et al.  Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration , 2006, Nature Genetics.

[143]  Johanna M Seddon,et al.  Evaluation of the clinical age-related maculopathy staging system. , 2006, Ophthalmology.

[144]  P. Tommila,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. , 2006, Molecular vision.

[145]  P. Mitchell,et al.  Dietary fatty acids and the 5-year incidence of age-related maculopathy. , 2006, Archives of ophthalmology.

[146]  R. Guymer,et al.  Analysis of the Y402H variant of the complement factor H gene in age-related macular degeneration. , 2006, Investigative ophthalmology & visual science.

[147]  J. Ott,et al.  Lack of an association of apolipoprotein E gene polymorphisms with familial age-related macular degeneration. , 2003, Archives of ophthalmology.

[148]  H. Kawakami,et al.  NO ASSOCIATION OF COMPLEMENT FACTOR H GENE POLYMORPHISM AND AGE-RELATED MACULAR DEGENERATION IN THE JAPANESE POPULATION , 2006, Retina.

[149]  C. McCarty,et al.  Iris colour, ethnic origin and progression of age‐related macular degeneration , 2003, Clinical & experimental ophthalmology.

[150]  Johanna M Seddon,et al.  Variation in complement factor 3 is associated with risk of age-related macular degeneration , 2007, Nature Genetics.

[151]  M. C. Leske,et al.  Features of Age-Related Macular Degeneration in a Black Population , 1995 .

[152]  T. Das,et al.  Analysis of CFH, TLR4, and APOE polymorphism in India suggests the Tyr402His variant of CFH to be a global marker for age-related macular degeneration. , 2006, Investigative ophthalmology & visual science.

[153]  G. Jensen,et al.  Risk factors for age-related maculopathy in a 14-year follow-up study: the Copenhagen City Eye Study. , 2005, Acta ophthalmologica Scandinavica.

[154]  S. Fisher,et al.  Assessment of the contribution of CFH and chromosome 10q26 AMD susceptibility loci in a Russian population isolate , 2006, British Journal of Ophthalmology.

[155]  Donna Arnett,et al.  Twin study of age-related macular degeneration , 2003, Ophthalmic epidemiology.

[156]  Albert Hofman,et al.  Epidemiology of age-related maculopathy: a review. , 2003, European journal of epidemiology.

[157]  Dissection of genomewide-scan data in extended families reveals a major locus and oligogenic susceptibility for age-related macular degeneration. , 2004, American journal of human genetics.

[158]  T. Maruo,et al.  Changes in causes of visual handicaps in Tokyo. , 1991, Japanese journal of ophthalmology.

[159]  R. Klein,et al.  The relationship between iris color, hair color, and skin sun sensitivity and the 10-year incidence of age-related maculopathy: the Beaver Dam Eye Study. , 2003, Ophthalmology.

[160]  R. Klein,et al.  The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. , 1997, Ophthalmology.

[161]  H. Taylor,et al.  Ultraviolet radiation and the eye: an epidemiologic study. , 1989, Transactions of the American Ophthalmological Society.

[162]  S. Santangelo,et al.  A genomewide scan for age-related macular degeneration provides evidence for linkage to several chromosomal regions. , 2003, American journal of human genetics.

[163]  S. Nilsson From basic to clinical research: a journey with the retina, the retinal pigment epithelium, the cornea, age-related macular degeneration and hereditary degenerations, as seen in the rear view mirror. , 2006, Acta ophthalmologica Scandinavica.

[164]  E. Souied,et al.  Y402H complement factor H polymorphism associated with exudative age-related macular degeneration in the French population. , 2005, Molecular vision.

[165]  J. Gilbert,et al.  Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6. , 2006, Investigative ophthalmology & visual science.