Investigating Genetic or Immune Factors in Age-Related Macular Degeneration

Utilizing novel genetics tools and analyses to identify new genetic or immune system risk factors or targets for the treatment of age-related macular degeneration by exploring diverse study populations Previous studies only included European populations to identify AMD genetic risk factors. We will utilize the power of diverse ancestry data via the International AMD Consortium to look for common novel risk/protective genetic factors in unstudied ancestries. Afterward, we will look at novel rare variants possibly present in small subsets, utilizing novel tools/data. Finally, we will look at the immune system’s contribution to AMD by identifying gene expression changes and variants influencing gene expression in monocytes or other white blood cells with a known contribution to AMD pathogenesis.

Age-related macular degeneration (AMD) is the leading cause of blindness over age 60, and involves genetics, the immune system, and the environment. Unexplored until today have been the genetic risk of developing AMD by using data from diverse ancestries, using new genetic reference panels, and investigating structural variants like insertions or deletions. The relationship between a person’s genetics and their immune system has also not been fully explored. Expression quantitative loci, or eQTLs, are genetic variants that influence the expression of one or more genes and their resultant proteins. We suggest to create a novel panel of immune cells, like monocytes and macrophages, to identify eQTLs related to risk or treatment response for AMD. We propose to use novel technological tools and diverse ancestry reference panels that were previously unavailable, to identify new genetic risk factors for AMD and possible new genetic or immune system targets for treatment of the disease. We will utilize the existing genetics of the International Age-Related Macular Degeneration Genomics Consortium, with over 50,000 samples, to investigate these issues on a large scale. Utilizing multiethnic participants will allow for discovery of rare genetic variants not previously investigated.

Undiscovered genetic variants in unrepresented ancestries may be novel risk or protective factors for AMD. Utilizing the large scale dataset of over 52,000 individuals of the IAMDGC to investigate genetic and immune factors for AMD could identify new pathways involved in AMD pathogenesis. Investigating the immune cells most known for their involvement in AMD and applying it to a large scale dataset allows both genetics and transcriptomics to collide in big data analysis for understanding the genetic architecture of AMD.

We hope this large scale genetic and transcriptomic analysis of AMD will allow for identification of novel pathways, understanding of pathogenesis and possible treatments for AMD, based on new variants. Underrepresented ancestries will be included and investigated for the first time, and rare variants that were not previously found may be identified, and then utilized for pharmacogenetics or other personalized medicine approaches. The further investigation of the immune system allows for a novel understanding of its relationship to AMD, and the pathways contributing to AMD disease.