Sharing of Genetic Association Signals by Age-Related Macular Degeneration and Alzheimer's Disease at Multiple Levels.

Age-related macular degeneration and Alzheimer's disease are closely related complex diseases that may share overlapping pathogenesis in gene networks. This study was conducted to investigate the genetic factors shared by both diseases. We analyzed genome-wide association studies' summary statistics from both diseases using a new platform known as functional mapping and annotation (FUMA) and a co-localization analysis. We obtained disease-related gene expression profile data from the Gene Expression Omnibus and analyzed these data using weighted gene co-expression network analysis. FUMA analysis and Bayesian co-localization analysis showed that ten genes on chromosome 7, one pathway (complement and coagulation cascade), and forty-two biological processes were common for both diseases. Among these ten genes, two protein-coding genes, two pseudogenes, and two RNA genes were, for the first time, identified to be associated with both diseases. Weighted gene co-expression network analysis identified 19 age-related macular degeneration hub genes and 19 Alzheimer's disease hub genes and revealed that these two diseases shared nine pathways and 63 biological processes. Using FUMA, co-localization analysis, and weighted gene co-expression network analysis, 10 genes on chromosome 7, 10 pathways, and 105 biological processes were found to be associated with the two degenerative diseases. This suggests that these10 genes and the hub genes of these modules associated with the shared pathways are potential diagnostic markers for both diseases.