gms | German Medical Science

Background: Age-related macular degeneration (AMD) is a severe condition in elderly people and is the leading cause of vision impairment in industrialized countries. Little is known, however, about the molecular biology underlying this disease and thus about targeted approaches to develop innovative treatment options. Deciphering the genetic architecture underlying AMD development but also progression of the disease once manifestations have already developed may shed light on pathways and target molecules to treat this devastating condition.

Methods: Common single nucleotide polymorphism (SNP)-based genetic association studies (GWAS) are suited to correlate genetic variation to any trait or disease of interest. Generally, 800.000 to 1.000.000 SNPs are directly genotyped throughout the genome in a disease/trait group and compared to a matched control population. Statistical analysis of allele frequencies between the two groups eventually leads to genome-wide significant data which allow pinpointing pathways and specific target genes suitable to address in future clinical studies.

Results: To date, the genetic risk to develop AMD has essentially been worked out. There are more than 34 genetic loci accounting for at least 52 independent genetic risk variants associated with late stage AMD and with major effects at the CFH and the ARMS2 / HTRA1 loci, respectively. Progression of AMD may be a more crucial medical trait to be addressed and may underlie its own genetic architecture. Progression can be understood in several ways and currently is focused on progression from early to late stages of AMD, progression from early to a specific late stage subtypes of AMD and progression of geographic atrophy lesion growth. Here, we are at the beginning to understand the genetic Background of the various progression traits.

Conclusions: Genetic studies have the potential to guide the development of therapeutic treatment by pointing to disease-associated pathways and genes. So far, we have become aware that the various aspects of disease development and progression will likely lead to different target genes which can now be addressed in novel therapeutic approaches and first clinical trials.