Linkage analysis for age-related macular degeneration supports a gene on chromosome 10q26

Age-related macular degeneration (AMD) is a retinal degenerative disease that is the leading cause of blindness worldwide in individuals over the age of 60. Although the etiology of AMD remains largely unknown, numerous studies have suggested both genetic and environmental influences. A previous study of affected multiplex families identified four chromosomal regions that potentially harbor AMD susceptibility genes. The purpose of our study was to further investigate these regions with additional microsatellite marker coverage in our independent data set.

We examined regions on chromosomes 1q, 9p, 10q, and 17q for genetic linkage in our 70 multiplex families (consisting of 133 affected sibpairs). Two point heterogeneity LOD score (HLOD) and nonparametric LOD score (MLS) analyses were performed for disease models defined by the most severe status in either eye. Conditional analyses were performed using apolipoprotein E (APOE) alleles as covariates in semiparametric LOD (LOD*) score calculations.

Regions on chromosomes 1q, 9p, and 17q did not provide evidence of linkage in our data set. However, markers D10S1230 and D10S1656 on chromosome 10q26 generated maximum HLOD scores of 1.52 and 1.13, respectively. Marker D10S1230 also generated an MLS score of 1.56 in stage 4 and 5 individuals. Controlling for the potential effect of the APOE-epsilon4 allele did not substantially alter these scores.

With the inclusion of this study, at least five AMD data sets provide support of genetic linkage to 10q26. Such consistency and confirmation of evidence strongly suggests that this region should be the subject of further detailed genomic efforts for the disease.