Drusen Characteristics As a Potential Genetic Marker for AMD

Journal Highlights

Investigative Ophthalmology & Visual Science
2022;63(8):17

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Osterman et al. set out to identify genetic-risk loci for retinal traits in an Amish population and to compare findings with the known-risk loci of age-related macular degeneration (AMD). In their study of more than 1,000 participants, six single-nucleotide polymorphisms (SNPs) met the criteria for genome-wide significance, and 48 others were potentially significant.

For this research, the investigators recruited residents of Amish communi­ties in Ohio, Indiana, and Pennsylvania. Eligible individuals were those over 50 years of age from families in which at least two members had early or inter­mediate AMD. The authors obtained a health history from each participant, conducted eye exams and genotyping, and applied genome-wide association analysis to determine the presence and degree of geographic atrophy (GA), drusen area, and drusen volume. The data were collected as part of the Amish Eye Study, which is designed to identify early predictors of progression to AMD in at-risk individuals. They compared their SNP findings with those of a previous genome-wide association study consisting mainly of individuals of European descent. They also applied a genetic risk score for AMD to predict the presence and quantity of the three retinal characteristics.

The final analysis set included 1,074 participants. After correction via the Benjamini-Hochberg model with a false discovery rate of 20%, the SNPs with a significant association with drusen area or volume were rs8125299, rs79746087, rs7028791, rs7850939, rs76316680, and rs17759824. The affected chromo­somes were 2, 4, 9, 19, and 20. The SNP findings did not correlate strongly with the known-risk SNPs for AMD, and the genetic risk score for AMD was highly predictive of the retinal findings except for GA area.

The authors noted that “whole genome sequencing could allow for better detection of rare variants within the genome-wide significant loci, as the Amish may demonstrate variation that differs from a general European ancestry population.” The underlying genetic component of drusen may differ from that of AMD, they said. Given the rela-tively high heritability of AMD, it is plausible that drusen could be inherited in a similar manner, as suspected in previous studies. Further research may improve the understanding of drusen as a biomarker for genetic risk of AMD, said the authors, who concluded that building this knowledge could lead to better screening and treatment strate­gies for AMD. 

The original article can be found here.