Age-related macular degeneration (AMD) is a progressive neurodegenerative disease and the leading cause of blindness in developed countries. Current genome-wide association studies (GWAS) for late-stage age-related macular degeneration are mainly single-marker-based approaches, which investigate one Single-Nucleotide Polymorphism (SNP) at a time and postpone the integration of inter-marker Linkage-disequilibrium (LD) information in the downstream fine mappings. Recent studies showed that directly incorporating inter-marker connection/correlation into variants detection can help discover novel marginally weak single-nucleotide polymorphisms, which are often missed in conventional genome-wide association studies, and can also help improve disease prediction accuracy. Single-marker analysis is performed first to detect marginally strong single-nucleotide polymorphisms. Then the whole-genome linkage-disequilibrium spectrum is explored and used to search for high-linkage-disequilibrium connected single-nucleotide polymorphism clusters for each strong single-nucleotide polymorphism detected. Marginally weak single-nucleotide polymorphisms are selected a joint linear discriminant model with the detected single-nucleotide polymorphism clusters. Prediction is made based on the selected strong and weak single-nucleotide polymorphisms. Several previously identified late-stage age-related macular degeneration susceptibility genes, for example, , , , , , are confirmed. Novel genes , , , and are discovered as marginally weak signals. Overall prediction accuracy of 76.8% and 73.2% was achieved with and without the inclusion of the identified marginally weak signals, respectively. Marginally weak single-nucleotide polymorphisms, detected from integrating inter-marker linkage-disequilibrium information, may have strong predictive effects on age-related macular degeneration. Detecting and integrating such marginally weak signals can help with a better understanding of the underlying disease-development mechanisms for age-related macular degeneration and more accurate prognostics.