Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late stage disease

Abecasis, Gonçalo R.; Yashar, Beverly M.; Zhao, Yi; Ghiavand, N.M.; Zareparsi, Sepideh; Branham, E.H.; Reddick, Adam C.; Trager, Edward H.; Yoshida, Shigeaki; Bahling, J.; Филиппова, Елена; Elner, Susan G.; Johnson, M.W.; Vine, Andrew K.; Sieving, Paul A.; Jacobson, SG; Richards, Julia E.; Swaroop, Anand

doi:10.1016/j.ajo.2004.07.009

Cited by 18 publications

(28 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Despite the diYculties in pursuing linkage analysis in AMD several studies found evidence of a susceptibility locus at Chromosome 1q32 (Abecasis et al 2004;Iyengar et al 2004;Klein et al 1998;Majewski et al 2003;Seddon et al 2003b;Weeks et al 2001). Subsequent analysis of this region led to the identiWcation of an association between AMD and the Y402H allele of the complement factor H gene.…”

Section: Cfhmentioning

confidence: 94%

Progress in defining the molecular biology of age related macular degeneration

Lotery

Trump

2007

Hum Genet

View full text Add to dashboard Cite

Age related macular degeneration (AMD) is an extremely prevalent complex genetic disorder. Its incidence rises exponentially in the elderly to a frequency of 1 in 2 in the general population by age 85. It affects approximately 25 million people and is the commonest cause of irreversible visual loss in the Western world. It is therefore a major public health problem. However, until recently its aetiology was unknown. Our understanding of both the molecular biology of AMD and the relevant clinical treatments has progressed dramatically in the last 2 years. Two genes of large effect have been identified which together contribute to over 70% of the population attributable risk of AMD. Treatments which inhibit expression of vascular endothelial growth factor have been developed which can rescue vision in the "wet" form of the disease. The association of complement factor H with AMD highlights the importance of the alternative complement pathway in the development of AMD whilst the pathophysiology of the serine protease HTRA1 is now under intensive study. This review will give an insight into these developments and will summarise our current knowledge of the molecular biology of AMD.

show abstract

Section: Cfhmentioning

confidence: 94%

Progress in defining the molecular biology of age related macular degeneration

Lotery

Trump

2007

Hum Genet

View full text Add to dashboard Cite

show abstract

“…97,98 Evidence of linkage has also been found in regions at chromosomes 1q, 2p, 3p, 4q, 10q, 12q and 16q as well as several other chromosomes in different populations. [91][92][93]99 A meta-analysis of genome-wide linkage studies in AMD has confirmed these candidate regions. In that study, the strongest evidence for an AMD susceptibility locus was found on chromosome 10q26, and the second most significant region identified was on chromosome 1q, which contains the CFH gene.…”

Section: Gene Identification Linkage Studiesmentioning

confidence: 77%

“…However, independent groups did not support the association of the Gln5345Arg variant in hemicentin-1 with AMD. 92,96 Mutations of other fibulin genes have also been associated with AMD. 97,98 Evidence of linkage has also been found in regions at chromosomes 1q, 2p, 3p, 4q, 10q, 12q and 16q as well as several other chromosomes in different populations.…”

Section: Gene Identification Linkage Studiesmentioning

confidence: 98%

Review of Genetics in Age Related Macular Degeneration

Montezuma

Sobrin

Seddon

2007

Seminars in Ophthalmology

View full text Add to dashboard Cite

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.

show abstract

“…Recent genetic studies linked variants within fibulin-6 with AMD, 41,42 although another study suggested that the disease locus is telomeric of fibulin-6. 43 EFEMP1 also shows a strong homology (approximately 35% identity) to members of the fibrillin family, 44 another extracellular matrix protein family characterized by the presence of tandem repeats of EGF domains. 45 Fibrillins are constituents of extracellular microfibrils.…”

Section: Efemp1 As the Disease Gene For Ml/dhrdmentioning

confidence: 98%

Association of EFEMP1 with malattia leventinese and age-related macular degeneration: a mini-review

Marmorstein

2004

Ophthalmic Genetics

View full text Add to dashboard Cite

Malattia leventinese (ML) or Doyne honeycomb retinal dystrophy (DHRD) was the first clinically and histopathologically described Mendelian maculopathy. The gene responsible for ML/DHRD, EFEMPI (fibulin-3/SI-5/FBNL) encodes a member of the fibulin family, a newly recognized family of extracellular matrix proteins. EFEMPImutations have not been found in age-related macular degeneration (AMD) patients despite the close phenotypic similarities between ML/DHRD and AMD. This non-correlating genotype/phenotype relationship between inherited and age-related conditions is typical for common age-related diseases. Biochemical pathways delineated in other diseases indicate that the gene associated with the inherited condition is nonetheless critical in age-related forms. This review summarizes current knowledge relating to ML/DHRD and EFEMPI,with discussion of why EFEMPI mutations are absent in AMD and how EFEMPI may be involved in the pathogenesis of ML/DHRD and AMD.

show abstract

Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late stage disease

Cited by 18 publications

References 41 publications

Progress in defining the molecular biology of age related macular degeneration

Progress in defining the molecular biology of age related macular degeneration

Review of Genetics in Age Related Macular Degeneration

Association of EFEMP1 with malattia leventinese and age-related macular degeneration: a mini-review

Contact Info

Product

Resources

About