Genetic association analysis of drusen progression

Joshua D. Hoffman, Mark J.J.P. Van Grinsven, Chun Li, Milam Brantley, Josephine McGrath, Anita Agarwal, William K. Scott, Stephen G. Schwartz, Jaclyn Kovach, Margaret Pericak-Vance, Clara I. Sanchez, Jonathan L. Haines

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


PURPOSE. Age-related macular degeneration is a common form of vision loss affecting older adults. The etiology of AMD is multifactorial and is influenced by environmental and genetic risk factors. In this study, we examine how 19 common risk variants contribute to drusen progression, a hallmark of AMD pathogenesis. METHODS. Exome chip data was made available through the International AMD Genomics Consortium (IAMDGC). Drusen quantification was carried out with color fundus photographs using an automated drusen detection and quantification algorithm. A genetic risk score (GRS) was calculated per subject by summing risk allele counts at 19 common genetic risk variants weighted by their respective effect sizes. Pathway analysis of drusen progression was carried out with the software package Pathway Analysis by Randomization Incorporating Structure. RESULTS. We observed significant correlation with drusen baseline area and the GRS in the age-related eye disease study (AREDS) dataset (q = 0.175, P = 0.006). Measures of association were not statistically significant between drusen progression and the GRS (P = 0.54). Pathway analysis revealed the cell adhesion molecules pathway as the most highly significant pathway associated with drusen progression (corrected P = 0.02). CONCLUSIONS. In this study, we explored the potential influence of known common AMD genetic risk factors on drusen progression. Our results from the GRS analysis showed association of increasing genetic burden (from 19 AMD associated loci) to baseline drusen load but not drusen progression in the AREDS dataset while pathway analysis suggests additional genetic contributors to AMD risk.

Original languageEnglish (US)
Pages (from-to)2225-2231
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Issue number4
StatePublished - Apr 1 2016


  • Age-related macular degeneration
  • Drusen
  • Genetic risk score analysis
  • Image analysis

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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