Age-related macular degeneration (AMD) is a leading cause of vision loss in people over 60 years. Previous genome-wide association studies (GWAS) have identified both comment and rare variants in association with AMD and earlier age of disease onset. However, the top variants identified in GWAS only accounts for only part of the phenotypic variation. Larger sample sizes are needed to identify more genetic variants and gene by environment interactions, which may contribute to increase the risk of AMD. In this project, we aim to 1) identify novel genetic variants and gene-environment interactions associated with AMD by performing GWAS in UK Biobank samples and meta-analyzing results from UK Biobank with our on-going genetic studies; and 2) investigate molecular mechanism and pathways underlying AMD by integrating AMD GWAS with molecular QTLs using Mendelian randomization, colocalization and network approaches. The proposed study will last three years. With completion of the proposed project, we will provide novel data with respect to novel genes and pathways which are putatively causal for AMD and how environmental factors can modify genetic effects on the disease. As such we will provide new evidence to design better strategies to improve AMD diagnosis, prevention and treatment.
