Examining Age-Related Macular Degeneration in the Amish

Abstract

Purpose: : Age-related ophthalmic diseases present a significant health problem with huge social and economic consequences. Over the past two years, multiple genes have been identified for age-related macular degeneration (AMD). However, these critical successes only partially explain the genetic etiology of AMD.

Methods: : We have undertaken a powerful complementary approach for finding additional genes involved in ophthalmic diseases by using a genetically isolated founder population, the Midwestern Amish communities of the US. These Amish communities are more homogeneous in both environmental and genetic exposures. We have ascertained nearly 1900 Amish individuals for participation in studies of diseases prominently seen in older populations. We have identified 118 individuals who have self-reported AMD. Taking advantage of ongoing work within our group, we have genotyped 58 of these individuals, along with 614 additional Amish individuals, using the Illumina Linkage Panel IVb. We performed 2-pt linkage analysis, using both dominant and recessive models, on 5,645 SNPs using the Superlink program.

Results: : Initial analysis identified 143 SNPs with lod scores > 1.0. Of these, 16 SNPs also demonstrated an uncorrected MQLS (more powerful quasi-likelihood score test) test pvalue of <=0.05. In addition to the SNPs within this panel, we genotyped several previously confirmed AMD variants: most notably, rs10490924 within LOC387715 and rs1061170 within CFH. The rs10490924 variant gave an MQLS pvalue of 0.017, suggesting involvement of LOC387715 in AMD risk within this isolated population. However, rs1061170 did not demonstrate evidence for either linkage or association within our study.

Conclusions: : These preliminary results, notably the significant association at rs10490924, demonstrate the promise of this approach, even using self-reports of AMD.

Keywords: age-related macular degeneration • genetics