Update on the role of genetics in the onset of age-related macular degeneration

Peter James Francis, Michael Klein

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Age-related macular degeneration (AMD), akin to other common age-related diseases, has a complex pathogenesis and arises from the interplay of genes, environmental factors, and personal characteristics. The past decade has seen very significant strides towards identification of those precise genetic variants associated with disease. That genes encoding proteins of the (alternative) complement pathway (CFH, C2, CFB, C3, CFI) are major players in etiology came as a surprise to many but has already lead to the development of therapies entering human clinical trials. Other genes replicated in many populations ARMS2, APOE, variants near TIMP3, and genes involved in lipid metabolism have also been implicated in disease pathogenesis. The genes discovered to date can be estimated to account for approximately 50% of the genetic variance of AMD and have been discovered by candidate gene approaches, pathway analysis, and latterly genome-wide association studies. Next generation sequencing modalities and meta-analysis techniques are being employed with the aim of identifying the remaining rarer but, perhaps, individually more significant sequence variations, linked to disease status. Complementary studies have also begun to utilize this genetic information to develop clinically useful algorithms to predict AMD risk and evaluate pharmacogenetics. In this article, contemporary commentary is provided on rapidly progressing efforts to elucidate the genetic pathogenesis of AMD as the field stands at the end of the first decade of the 21st century.

Original languageEnglish (US)
Pages (from-to)1127-1133
Number of pages7
JournalClinical Ophthalmology
Volume5
Issue number1
StatePublished - 2011

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Macular Degeneration
Genes
Alternative Complement Pathway
Genome-Wide Association Study
Pharmacogenetics
Lipid Metabolism
Meta-Analysis
Clinical Trials
Population
Proteins

Keywords

  • AMD
  • Complex disease
  • Genes
  • Susceptibility

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Update on the role of genetics in the onset of age-related macular degeneration. / Francis, Peter James; Klein, Michael.

In: Clinical Ophthalmology, Vol. 5, No. 1, 2011, p. 1127-1133.

Research output: Contribution to journalArticle

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