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

Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways.

[1]  Á. Fekete,et al.  Analysis of complement factor H Y402H, LOC387715, HTRA1 polymorphisms and ApoE alleles with susceptibility to age‐related macular degeneration in Hungarian patients , 2011, Acta ophthalmologica.

[2]  Kang Zhang,et al.  Genetics of Age-Related Macular Degeneration , 2011 .

[3]  D. Chasman,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. , 2010, Archives of ophthalmology.

[4]  E. Eichler,et al.  Phenotypic variability and genetic susceptibility to genomic disorders. , 2010, Human molecular genetics.

[5]  R. Guymer,et al.  C-reactive protein levels and complement factor H polymorphism interaction in age-related macular degeneration and its progression. , 2010, Ophthalmology.

[6]  B. Rosner,et al.  Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration. , 2010, Ophthalmology.

[7]  Y. Hathout,et al.  Identification of novel substrates for the serine protease HTRA1 in the human RPE secretome. , 2010, Investigative ophthalmology & visual science.

[8]  Agus Salim,et al.  The discovery of human genetic variations and their use as disease markers: past, present and future , 2010, Journal of Human Genetics.

[9]  K. Horie-Inoue,et al.  Phenotype and genotype characteristics of age-related macular degeneration in a Japanese population. , 2010, Ophthalmology.

[10]  Margaret A. Pericak-Vance,et al.  Genetic variants near TIMP3 and high-density lipoprotein–associated loci influence susceptibility to age-related macular degeneration , 2010, Proceedings of the National Academy of Sciences.

[11]  Gary C. Brown,et al.  Analysis of six genetic risk factors highly associated with AMD in the region surrounding ARMS2 and HTRA1 on chromosome 10, region q26. , 2010, Investigative ophthalmology & visual science.

[12]  Muin J Khoury,et al.  Evaluation of the discriminative accuracy of genomic profiling in the prediction of common complex diseases , 2010, European Journal of Human Genetics.

[13]  Fei Ji,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 , 2010, Vision Research.

[14]  Don H. Anderson,et al.  The pivotal role of the complement system in aging and age-related macular degeneration: Hypothesis re-visited , 2010, Progress in retinal and eye research.

[15]  Eric N Brown,et al.  Complement, age-related macular degeneration and a vision of the future. , 2010, Archives of ophthalmology.

[16]  J. Haines,et al.  Analysis of the indel at the ARMS2 3′UTR in age-related macular degeneration , 2010, Human Genetics.

[17]  P. Zipfel,et al.  DEAP-HUS: Deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome , 2010, Pediatric Nephrology.

[18]  C. Patterson,et al.  Complement Component 3: an assessment of association with AMD and analysis of gene-gene and gene-environment interactions in a Northern Irish cohort , 2010, Molecular vision.

[19]  Ningli Wang,et al.  Noncoding variant in the complement factor H gene and risk of exudative age-related macular degeneration in a Chinese population. , 2010, Investigative ophthalmology & visual science.

[20]  H. Hense,et al.  Susceptibility genes and progression in age-related maculopathy: a study of single eyes. , 2010, Investigative ophthalmology & visual science.

[21]  Dean Y. Li,et al.  Genetic and Functional Dissection of HTRA1 and LOC387715 in Age-Related Macular Degeneration , 2010, PLoS genetics.

[22]  P. Barlow,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. , 2010, Blood.

[23]  A. Lusis,et al.  Cardiovascular networks: systems-based approaches to cardiovascular disease. , 2010, Circulation.

[24]  J. Bena,et al.  Proteomic and genomic biomarkers for age-related macular degeneration. , 2010, Advances in experimental medicine and biology.

[25]  Aaron Y. Lee,et al.  Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration , 2009, Molecular vision.

[26]  Hakon Hakonarson,et al.  Genome-wide association studies in type 1 diabetes, inflammatory bowel disease and other immune-mediated disorders. , 2009, Seminars in immunology.

[27]  P. Mitchell,et al.  Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples. , 2009, Investigative ophthalmology & visual science.

[28]  J. Błasiak,et al.  Association between vascular endothelial growth factor gene polymorphisms and age-related macular degeneration in a Polish population. , 2009, Experimental and molecular pathology.

[29]  Ivana K. Kim,et al.  Comprehensive analysis of complement factor H and LOC387715/ARMS2/HTRA1 variants with respect to phenotype in advanced age-related macular degeneration. , 2009, American journal of ophthalmology.

[30]  H. Hense,et al.  Variations in five genes and the severity of age-related macular degeneration: results from the Muenster aging and retina study , 2009, Eye.

[31]  S. O’Rahilly,et al.  Human genetics illuminates the paths to metabolic disease , 2009, Nature.

[32]  M. López-Trascasa,et al.  Characterization of complement factor H-related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome. , 2009, Blood.

[33]  J. Crabb,et al.  Synthesis and structural characterization of carboxyethylpyrrole-modified proteins: mediators of age-related macular degeneration. , 2009, Bioorganic & medicinal chemistry.

[34]  Lars Bertram,et al.  Genome-wide association studies in Alzheimer's disease. , 2009, Human molecular genetics.

[35]  Judy H. Cho,et al.  Finding the missing heritability of complex diseases , 2009, Nature.

[36]  R. Mayeux,et al.  Use of Genetic Variation as Biomarkers for Alzheimer's Disease , 2009, Annals of the New York Academy of Sciences.

[37]  A. Negi,et al.  SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy , 2009, Molecular vision.

[38]  A. Gubitz,et al.  Mining the genome for susceptibility to complex neurological disorders. , 2009, Current molecular medicine.

[39]  Anand Swaroop,et al.  Unraveling a multifactorial late-onset disease: from genetic susceptibility to disease mechanisms for age-related macular degeneration. , 2009, Annual review of genomics and human genetics.

[40]  J. Lupski,et al.  Mechanisms of change in gene copy number , 2009, Nature Reviews Genetics.

[41]  H. Bi,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 , 2009, Retina.

[42]  J. Haines,et al.  Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria. , 2009, Investigative ophthalmology & visual science.

[43]  B. Fridley,et al.  Complement component 3 (C3) haplotypes and risk of advanced age-related macular degeneration. , 2009, Investigative ophthalmology & visual science.

[44]  R. Yamada,et al.  ARMS2 (LOC387715) variants in Japanese patients with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. , 2009, American journal of ophthalmology.

[45]  A. Lewin.  Geographic atrophy in age-related macular degeneration and TLR3. , 2009, The New England journal of medicine.

[46]  K. Stefánsson,et al.  Geographic atrophy in age-related macular degeneration and TLR3. , 2009, The New England journal of medicine.

[47]  P. Mitchell,et al.  Mitochondrial DNA Variants of Respiratory Complex I that Uniquely Characterize Haplogroup T2 Are Associated with Increased Risk of Age-Related Macular Degeneration , 2009, PloS one.

[48]  R. Nagaraj,et al.  Plasma Protein Pentosidine and Carboxymethyllysine, Biomarkers for Age-related Macular Degeneration* , 2009, Molecular & Cellular Proteomics.

[49]  Johanna M Seddon,et al.  Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. , 2009, Investigative ophthalmology & visual science.

[50]  S. Cichon,et al.  Genomewide association studies: history, rationale, and prospects for psychiatric disorders. , 2009, The American journal of psychiatry.

[51]  K. Frazer,et al.  Human genetic variation and its contribution to complex traits , 2009, Nature Reviews Genetics.

[52]  C. Semsarian,et al.  Multiple Mutations in Genetic Cardiovascular Disease: A Marker of Disease Severity? , 2009, Circulation. Cardiovascular genetics.

[53]  B. Gold,et al.  Multilocus analysis of age-related macular degeneration , 2009, European Journal of Human Genetics.

[54]  M. Halushka,et al.  Tissue Inhibitor of Matrix Metalloproteinase-3 Levels in the Extracellular Matrix of Lung, Kidney, and Eye Increase With Age , 2009, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[55]  R. Klein,et al.  Serum cystatin C level, kidney disease markers, and incidence of age-related macular degeneration: the Beaver Dam Eye Study. , 2009, Archives of ophthalmology.

[56]  J. Bena,et al.  Assessing Susceptibility to Age-related Macular Degeneration with Proteomic and Genomic Biomarkers* , 2009, Molecular & Cellular Proteomics.

[57]  B. Rosner,et al.  Peripheral retinal drusen and reticular pigment: association with CFHY402H and CFHrs1410996 genotypes in family and twin studies. , 2009, Investigative ophthalmology & visual science.

[58]  John P A Ioannidis,et al.  Prediction of Cardiovascular Disease Outcomes and Established Cardiovascular Risk Factors by Genome-Wide Association Markers , 2009, Circulation. Cardiovascular genetics.

[59]  Daniel E. Weeks,et al.  Interpretation of Genetic Association Studies: Markers with Replicated Highly Significant Odds Ratios May Be Poor Classifiers , 2009, PLoS genetics.

[60]  Wen-zhen Yu,et al.  Association of C3 Gene Polymorphisms with Neovascular Age-Related Macular Degeneration in a Chinese Population , 2009, Current eye research.

[61]  S. Tsuji,et al.  Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. , 2009, The New England journal of medicine.

[62]  M. Daly,et al.  Variation near complement factor I is associated with risk of advanced AMD , 2009, European Journal of Human Genetics.

[63]  J. Ott,et al.  Polymorphisms in C2, CFB and C3 are associated with progression to advanced age related macular degeneration associated with visual loss , 2008, Journal of Medical Genetics.

[64]  A. Hofman,et al.  Polymorphisms in the vascular endothelial growth factor gene and risk of age-related macular degeneration: the Rotterdam Study. , 2008, Ophthalmology.

[65]  G. Parmigiani,et al.  Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. , 2008, The New England journal of medicine.

[66]  J. Naggert,et al.  Allelic variance between GRM6 mutants, Grm6nob3 and Grm6nob4 results in differences in retinal ganglion cell visual responses , 2008, The Journal of physiology.

[67]  J. Hoh,et al.  Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on AMD in a Caucasian population , 2008, Molecular vision.

[68]  Martin Oppermann,et al.  Systemic Complement Activation in Age-Related Macular Degeneration , 2008, PloS one.

[69]  Ivana K. Kim,et al.  Alleles in the HtrA serine peptidase 1 gene alter the risk of neovascular age-related macular degeneration. , 2008, Ophthalmology.

[70]  R. Yamada,et al.  Manganese superoxide dismutase gene (SOD2) polymorphism and exudative age-related macular degeneration in the Japanese population. , 2008, American journal of ophthalmology.

[71]  C. Nordgaard,et al.  Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of age-related macular degeneration. , 2008, Investigative ophthalmology & visual science.

[72]  S. Fisher,et al.  Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA , 2008, Nature Genetics.

[73]  G. Muscat,et al.  The orphan nuclear receptor, RORalpha, regulates gene expression that controls lipid metabolism: staggerer (SG/SG) mice are resistant to diet-induced obesity. , 2008, The Journal of biological chemistry.

[74]  J. Haines,et al.  C3 R102G polymorphism increases risk of age-related macular degeneration. , 2008, Human molecular genetics.

[75]  Ivana K. Kim,et al.  The NEI/NCBI dbGAP database: Genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration , 2008, BMC Medical Genetics.

[76]  D. Weeks,et al.  C2 and CFB Genes in Age-Related Maculopathy and Joint Action with CFH and LOC387715 Genes , 2008, PloS one.

[77]  A. Hamsten,et al.  Identifying the susceptibility genes for coronary artery disease: from hyperbole through doubt to cautious optimism , 2008, Journal of internal medicine.

[78]  T. Seya,et al.  TLR3: interferon induction by double-stranded RNA including poly(I:C). , 2008, Advanced drug delivery reviews.

[79]  P. Mitchell,et al.  The LOC387715 polymorphism, inflammatory markers, smoking, and age-related macular degeneration. A population-based case-control study. , 2008, Ophthalmology.

[80]  E. Birney,et al.  Approaches to comparative sequence analysis: towards a functional view of vertebrate genomes , 2008, Nature Reviews Genetics.

[81]  Katherine M. James,et al.  Toll-like receptor polymorphisms and age-related macular degeneration. , 2008, Investigative ophthalmology & visual science.

[82]  P. Zipfel,et al.  Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. , 2008, Blood.

[83]  N. Camp,et al.  Further mapping of 10q26 supports strong association of HTRA1 polymorphisms with age-related macular degeneration , 2008, Vision Research.

[84]  J. Haines,et al.  Phenotype analysis of patients with the risk variant LOC387715 (A69S) in age-related macular degeneration. , 2007, American journal of ophthalmology.

[85]  R. T. Smith,et al.  Comprehensive analysis of the candidate genes CCL2, CCR2, and TLR4 in age-related macular degeneration. , 2008, Investigative ophthalmology & visual science.

[86]  B. Chang,et al.  Expression of VLDLR in the retina and evolution of subretinal neovascularization in the knockout mouse model's retinal angiomatous proliferation. , 2008, Investigative ophthalmology & visual science.

[87]  M. Brantley,et al.  Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab. , 2007, Ophthalmology.

[88]  Gonçalo R. Abecasis,et al.  A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration , 2007, Proceedings of the National Academy of Sciences.

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

[90]  A. Hofman,et al.  C-reactive protein level and risk of aging macula disorder: The Rotterdam Study. , 2007, Archives of ophthalmology.

[91]  P. Mitchell,et al.  Mitochondrial DNA haplogroups and age-related maculopathy. , 2007, Archives of ophthalmology.

[92]  J. Haines,et al.  Protective effect of complement factor B and complement component 2 variants in age-related macular degeneration. , 2007, Human molecular genetics.

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

[94]  G. Abecasis,et al.  Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits. , 2007, Human molecular genetics.

[95]  J. Lupski,et al.  Genomic rearrangements and sporadic disease , 2007, Nature Genetics.

[96]  P. Mitchell,et al.  The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples. , 2007, Investigative ophthalmology & visual science.

[97]  R. Klein,et al.  Overview of Progress in the Epidemiology of Age-Related Macular Degeneration , 2007, Ophthalmic epidemiology.

[98]  J. Haines,et al.  Neovascular age-related macular degeneration and its association with LOC387715 and complement factor H polymorphism. , 2007, Archives of ophthalmology.

[99]  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.

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

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

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

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

[104]  J. Escardo,et al.  VEGF polymorphisms are associated with neovascular age-related macular degeneration. , 2006, Human molecular genetics.

[105]  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.

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

[107]  Johanna M Seddon,et al.  Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration , 2006, Nature Genetics.

[108]  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.

[109]  Baitang Ning,et al.  Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[110]  C. Reilly,et al.  The proteome of central and peripheral retina with progression of age-related macular degeneration. , 2006, Investigative ophthalmology & visual science.

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

[112]  R. Yamada,et al.  No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese , 2006, Human Genetics.

[113]  R. Kuhn,et al.  RORA, a large common fragile site gene, is involved in cellular stress response , 2006, Oncogene.

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

[115]  A. Hofman,et al.  A common polymorphism in the complement factor H gene is associated with increased risk of myocardial infarction: the Rotterdam Study. , 2006, Journal of the American College of Cardiology.

[116]  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.

[117]  Alston Callahan,et al.  The role of inflammation in the pathogenesis of age-related macular degeneration. , 2006, Survey of ophthalmology.

[118]  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.

[119]  Don H. Anderson,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 , 2006, Annals of medicine.

[120]  J L McRae,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) , 2005, Journal of Medical Genetics.

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

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

[123]  A. Swaroop,et al.  Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration. , 2005, Ophthalmology.

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

[125]  S. Fisher,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 .

[126]  Ronald Klein,et al.  A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. , 2005, Archives of ophthalmology.

[127]  R. Klein,et al.  Prevalence of age-related macular degeneration in a population-based sample of Hispanic people in Arizona: Proyecto VER. , 2005, Archives of ophthalmology.

[128]  H. Deng,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 , 2005, Journal of Medical Genetics.

[129]  R. Klein,et al.  Genome-wide analyses demonstrate novel loci that predispose to drusen formation. , 2005, Investigative ophthalmology & visual science.

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

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

[132]  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.

[133]  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.

[134]  G. Abecasis,et al.  Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration. , 2005, Human molecular genetics.

[135]  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.

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

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

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

[139]  I. Young,et al.  Association study of detoxification genes in age related macular degeneration , 2005, British Journal of Ophthalmology.

[140]  Leslie Hyman,et al.  A Simplified Severity Scale for Age-Related Macular Degeneration , 2005 .

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

[142]  R. Guymer,et al.  Analysis of the EFEMP1 gene in individuals and families with early onset drusen , 2005, Eye.

[143]  Elizabeth J Johnson.  Obesity, lutein metabolism, and age-related macular degeneration: a web of connections. , 2005, Nutrition reviews.

[144]  R. Guymer,et al.  Association of the M55L and Q192R paraoxonase gene polymorphisms with age-related macular degeneration. , 2004, American journal of ophthalmology.

[145]  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.

[146]  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.

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

[148]  Silke Schmidt,et al.  Ordered subset linkage analysis supports a susceptibility locus for age-related macular degeneration on chromosome 16p12 , 2004, BMC Genetics.

[149]  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.

[150]  Robyn H Guymer,et al.  The epsilon2 and epsilon4 alleles of the apolipoprotein gene are associated with age-related macular degeneration. , 2004, Investigative ophthalmology & visual science.

[151]  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.

[152]  P. Jong.  Prevalence of age-related macular degeneration in the United States. , 2004 .

[153]  R. Klein,et al.  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.

[154]  J. Mariani,et al.  The “CholesteROR” Protective Pathway in the Vascular System , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[155]  G. Abecasis,et al.  Age-Related Macular Degeneration: A High-Resolution Genome Scan for Susceptibility Loci in a Population Enriched for Late-Stage Disease , 2004 .

[156]  J. Haines,et al.  Linkage analysis for age-related macular degeneration supports a gene on chromosome 10q26. , 2004, Molecular vision.

[157]  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.

[158]  A. Thomson,et al.  mRNA Stability and the Control of Gene Expression: Implications for Human Disease , 2002, Neurochemical Research.

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

[160]  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.

[161]  A whole-genome screen of a quantitative trait of age-related maculopathy in sibships from the Beaver Dam Eye Study. , 2003, American journal of human genetics.

[162]  Richard Mayeux,et al.  The Genetics of Adult-Onset Neuropsychiatric Disease: Complexities and Conundra? , 2003, Science.

[163]  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.

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

[165]  Martin Friedlander,et al.  MOUSE MODEL OF SUBRETINAL NEOVASCULARIZATION WITH CHOROIDAL ANASTOMOSIS , 2003, Retina.

[166]  R. Klein,et al.  Relation of statin use to the 5-year incidence and progression of age-related maculopathy. , 2003, Archives of ophthalmology.

[167]  J. Gilbert,et al.  Detailed analysis of allelic variation in the ABCA4 gene in age-related maculopathy. , 2003, Investigative ophthalmology & visual science.

[168]  A. Zwinderman,et al.  Variants of Toll-Like Receptor 4 Modify the Efficacy of Statin Therapy and the Risk of Cardiovascular Events , 2003, Circulation.

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

[170]  L. Claesson‐Welsh,et al.  A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2 , 2003, Nature Medicine.

[171]  P. Allen,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 , 2002, Clinical & experimental ophthalmology.

[172]  Masaru Miyagi,et al.  Drusen proteome analysis: An approach to the etiology of age-related macular degeneration , 2002, Proceedings of the National Academy of Sciences of the United States of America.

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

[174]  A. Nesburn,et al.  Alu DNA polymorphism in ACE gene is protective for age-related macular degeneration. , 2002, Biochemical and biophysical research communications.

[175]  J. Hardy,et al.  The Amyloid Hypothesis of Alzheimer ’ s Disease : Progress and Problems on the Road to Therapeutics , 2009 .

[176]  D. Schwartz,et al.  Toll-like receptor 4 polymorphisms and atherogenesis. , 2002, The New England journal of medicine.

[177]  Harold Snieder,et al.  Genetic influence on early age-related maculopathy: a twin study. , 2002, Ophthalmology.

[178]  R. Nitsch,et al.  CST3 genotype associated with exudative age related macular degeneration , 2002, The British journal of ophthalmology.

[179]  J. Lupski,et al.  Genotype-phenotype analysis of ABCR variants in macular degeneration probands and siblings. , 2002, Investigative ophthalmology & visual science.

[180]  S. Richer,et al.  Serum Iron, Transferrin Saturation, Ferritin, and Dietary Data in Age-Related Macular Degeneration , 2002, American journal of therapeutics.

[181]  J. Haines,et al.  A pooled case-control study of the apolipoprotein E (APOE) gene in age-related maculopathy , 2002, Ophthalmic genetics.

[182]  J. Mariani,et al.  Increased Ischemia-Induced Angiogenesis in the Staggerer Mouse, a Mutant of the Nuclear Receptor Ror&agr; , 2001, Circulation Research.

[183]  M. Margaglione,et al.  Apolipoprotein E Polymorphisms in Age-Related Macular Degeneration in an Italian Population , 2001, Ophthalmic Research.

[184]  A. Hutchinson,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. , 2001, Ophthalmology.

[185]  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.

[186]  D. Weeks,et al.  Age-related maculopathy: an expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions. , 2001, American journal of ophthalmology.

[187]  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.

[188]  T. Yoshikawa,et al.  Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as possible risk factors for exudative age-related macular degeneration. , 2001, American journal of ophthalmology.

[189]  D. Pollen,et al.  Distinguishable effects of Presenilin-1 and APP717 mutations on amyloid plaque deposition , 2001, Neurobiology of Aging.

[190]  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.

[191]  V. Sheffield,et al.  An analysis of allelic variation in the ABCA4 gene. , 2001, Investigative ophthalmology & visual science.

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

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

[194]  M. Akimoto,et al.  Lack of association of mutations of the bestrophin gene with age-related macular degeneration in non-familial Japanese patients , 2001, Graefe's Archive for Clinical and Experimental Ophthalmology.

[195]  J L Haines,et al.  Association of the apolipoprotein E gene with age-related macular degeneration: possible effect modification by family history, age, and gender. , 2000, Molecular vision.

[196]  S. Sonoda,et al.  Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration. , 2000, American journal of ophthalmology.

[197]  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.

[198]  A. Saunders.  Apolipoprotein E and Alzheimer Disease: An Update on Genetic and Functional Analyses , 2000, Journal of neuropathology and experimental neurology.

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

[200]  G. Oberto,et al.  Alzheimer's disease: transgenic mouse models and drug assessment. , 2000, Pharmacological research.

[201]  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.

[202]  C. Pang,et al.  The Apolipoprotein E ε4 Allele Is Unlikely to Be a Major Risk Factor of Age-Related Macular Degeneration in Chinese , 2000, Ophthalmologica.

[203]  D. Weeks,et al.  A full genome scan for age-related maculopathy. , 2000, Human molecular genetics.

[204]  V. Sheffield,et al.  Allelic variation in the VMD2 gene in best disease and age-related macular degeneration. , 2000, Investigative ophthalmology & visual science.

[205]  B. Lorenz,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 , 2000, European Journal of Human Genetics.

[206]  C. Klaver,et al.  The genetics of age-related macular degeneration. , 1999, Molecular vision.

[207]  J. Gilbert,et al.  Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration. , 1999, Ophthalmology.

[208]  A. Munnich,et al.  Age-related macular degeneration in grandparents of patients with Stargardt disease: genetic study. , 1999, American journal of ophthalmology.

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

[210]  V. Sheffield,et al.  A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy , 1999, Nature Genetics.

[211]  M. Metzker,et al.  Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies , 1999, Human Genetics.

[212]  K. Cruickshanks.  Sunlight exposure and risk of lens opacities in a population-based study. , 1998, Archives of ophthalmology.

[213]  V. Sheffield,et al.  Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration , 1998, Nature Genetics.

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

[215]  D D Duncan,et al.  Sunlight exposure and risk of lens opacities in a population-based study: the Salisbury Eye Evaluation project. , 1998, JAMA.

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

[217]  A. Hofman,et al.  Genetic association of apolipoprotein E with age-related macular degeneration. , 1998, American journal of human genetics.

[218]  T. Südhof,et al.  Synapsin III, a Novel Synapsin with an Unusual Regulation by Ca2+ * , 1998, The Journal of Biological Chemistry.

[219]  A. Munnich,et al.  The γ e4 allele of the apolipoprotein E gene as a potential protective factor for exudative age-related macular degeneration , 1998 .

[220]  P. Mitchell,et al.  Serum beta carotene, alpha tocopherol, and age-related maculopathy: the Blue Mountains Eye Study. , 1997, American journal of ophthalmology.

[221]  Paul S. Bernstein,et al.  Mutation of the Stargardt Disease Gene (ABCR) in Age-Related Macular Degeneration , 1997 .

[222]  J. Haines,et al.  Exclusion of TIMP3 as a candidate locus in age-related macular degeneration. , 1997, Investigative ophthalmology & visual science.

[223]  E. Zrenner,et al.  Evaluation of the gene encoding the tissue inhibitor of metalloproteinases-3 in various maculopathies. , 1997, Investigative ophthalmology & visual science.

[224]  J M Seddon,et al.  Familial aggregation of age-related maculopathy. , 1997, American journal of ophthalmology.

[225]  J. Rommens,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 , 1995, Nature.

[226]  M. S. Brown,et al.  Normal plasma lipoproteins and fertility in gene-targeted mice homozygous for a disruption in the gene encoding very low density lipoprotein receptor. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[227]  V. Sheffield,et al.  A peripherin/retinal degeneration slow mutation (Pro-210-Arg) associated with macular and peripheral retinal degeneration. , 1995, Ophthalmology.

[228]  C. M. Kemp,et al.  RDS gene mutations causing retinitis pigmentosa or macular degeneration lead to the same abnormality in photoreceptor function. , 1994, Investigative ophthalmology & visual science.

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

[230]  D. Pollen,et al.  Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14 , 1992, Nature Genetics.

[231]  J. Weber,et al.  Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14. , 1992, Science.

[232]  B. Munoz,et al.  Visible light and risk of age-related macular degeneration. , 1990, Transactions of the American Ophthalmological Society.

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

[234]  H. Arvilommi.  Capacity of complement C3 phenotypes to bind on to mononuclear cells in man , 1974, Nature.