International Advancing genomics through the AMD Genomics Consortium (IAMDGC)

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Age-related macular degeneration (AMD) is a leading cause of vision loss in older Americans and severely impacts the independence, quality of life, and healthcare costs for those afflicted and their families. Genetic variation has a major influence on AMD, but only about half of the heritability is currently understood. Understanding the genetic architecture of AMD is critical for developing better treatments for AMD. The International AMD Genomics Consortium (IAMDGC) has assembled 33 research groups and over the past four years of this grant has enabled significant progress by extending the number of known risk loci and implicating new biological pathways. This renewal extends these efforts to multiple genetic ancestries, study designs, and more detailed phenotypic data. We propose the following aims: 1) Continue to expand the IAMDGC resource with new datasets. We have added seven new collaborators and now have access to data from >100,000 participants. 2) Use universal hubs to process and share genomic, phenotypic, and biomarker data. Regeneron Pharmaceuticals has agreed to conduct whole exome sequencing on approximately 40,000 participants at no cost to the grant. By statistical imputation on the remaining GWASed samples, we will create an extremely large dataset. We will continue to house the data in two analytic hubs (US and Europe) to simplify access and provide computational and analytic support. 3) Perform detailed analyses on the extensive resulting dataset. The dataset (87,542 cases/controls and 13,766 related individuals in nearly 6,000 families) enables testing of numerous genetic hypotheses underlying clinical subtypes, biomarkers, effects of rare variants, and variability in the genetic architecture across ancestries. The initial processing and analysis of the combined genomic data will be overseen through this application and results will be available to all members. We have an efficient process allowing members to propose additional studies and the broader research community to access these data and computational and analytical support through the appropriate analytic hub. 4) Support the logistics and administration of the IAMDGC. Successful collaboration requires constant communication and support. We will continue our yearly IAMDGC-specific face-to-face meeting, a second half- day meeting for those attending the ARVO annual meeting, and regular teleconference calls. Our goal is to greatly advance the understanding of AMD pathophysiology (using genomics as our foundational guide) and thus speed the development of better treatments and/or preventions of AMD.