We identified elevated systemic concentrations of total FHR-1, total FHR-2, FHR-1/1 dimers, FHR-1/2 dimers, FHR-2/2 dimers, FHR-3, and FHR-4A in individuals with AMD, and we found associations of all FHR concentrations with common AMD genetic variants and haplotypes at the extended CFH locus. Here, CFHR1 is linked to age-related macular degeneration.