A full genome scan for age-related maculopathy

Age-related macular degeneration or age-related maculopathy (ARM) is a majo r public health issue, as it is the leading cause of irreversible vision lo ss in the elderly in the Western world. Using three diagnostic models, we h ave genotyped markers in 16 plausible candidate regions and have carried ou t a genome-wide screen for ARM susceptibility loci. A panel of 225 ARM fami lies comprising up to 212 affected sib pairs was genotyped for 386 markers, Under our most stringent diagnostic model, the regions with the strongest evidence of linkage were on chromosome 9 near D9S301 and on 10 near D10S123 0, with peak multipoint heterogeneity LOD scores (HLOD) of 1.87 and 1.42 an d peak Gene-Hunter-Plus non-parametric LOD scores (GHP LOD) of 1.69 and 1.8 3. After expanding our initial set of families to 364 ARM families with up to 329 affected sib pairs, the linkage signal on chromosome 9 vanished, whi le the chromosome 10 signal decreased to a GHP LOD of about 1.0, with a Sim IBD P-value of 0.008 under the broadest diagnostic model with marker D10S12 36. After error filtration, the GHP LOD increased to 1.27 under our most st ringent model and 1.42 under our broadest model, peaking near D10S1236. Thi s peak was seen consistently across all three diagnostic models. Our analys es also excluded up to nine different candidate regions and identified a fe w other regions of potential linkage, suitable for further studies. Of part icular interest was the region on chromosome 5 near D5S1480, where a reason able candidate gene, glutathione peroxidase 3, resides.