A Validated Phenotyping Algorithm for Genetic Association Studies in Age-related Macular Degeneration

  title={A Validated Phenotyping Algorithm for Genetic Association Studies in Age-related Macular Degeneration},
  author={Joseph M. Simonett and Mahsa A. Sohrab and Jennifer Allen Pacheco and Loren L. Armstrong and Margarita Rzhetskaya and Maureen E. Smith and M. Geoffrey Hayes and Amani A. Fawzi},
  journal={Scientific Reports},
Age-related macular degeneration (AMD), a multifactorial, neurodegenerative disease, is a leading cause of vision loss. With the rapid advancement of DNA sequencing technologies, many AMD-associated genetic polymorphisms have been identified. Currently, the most time consuming steps of these studies are patient recruitment and phenotyping. In this study, we describe the development of an automated algorithm to identify neovascular (wet) AMD, non-neovascular (dry) AMD and control subjects using… 
4 Citations
Genetics and the Variable Phenotype of Age-Related Macular Degeneration.
3 major genetic risk variants for AMD in the CFH, ARMS2, and C3 genes are evaluated and their association with pretreatment demographic characteristics and imaging findings in patients with nvAMD is examined, creating new avenues and uncover major challenges in the field of AMD genetics.
Genetically-guided algorithm development and sample size optimization for age-related macular degeneration cases and controls in electronic health records from the VA Million Veteran Program.
This two-phase approach to developing research-grade case/control variables for AMD genomic studies capitalizes on established genetic associations resulting in high precision and optimized sample sizes, an approach that can be applied to other large-scale biobanks linked to EHRs for precision medicine research.
Machine Learning Method to Establish the Connection Between Age Related Macular Degeneration and Some Genetic Variations
A machine-learning based analysis is presented to determine the relation of three single nucleotide SNPs and the AMD disease and determine the best set of features for the classification process.
Population-Based Penetrance of Deleterious Clinical Variants.
In 2 large biobank cohorts, the estimated penetrance of pathogenic/loss-of-function variants was variable but generally low, and was heterogeneous even in known disease predisposition genes.


Clinical validation of a genetic model to estimate the risk of developing choroidal neovascular age-related macular degeneration
A predictive model based solely on genetic markers was developed and avoided inclusion of self-reported variables or non-static factors that might otherwise introduce inaccuracies in calculating individual risk estimates, comparable with metrics reported with earlier testing models that included environmental risk factors.
Seven New Loci Associated with Age-Related Macular Degeneration
A collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry, identifies 19 loci associated at P < 5 × 10−8, which show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis.
Complement C3 variant and the risk of age-related macular degeneration.
The common functional polymorphism rs2230199 in the C3 gene, corresponding to the electrophoretic variants C3S and C3F, was strongly associated with age-related macular degeneration in both the English group and the Scottish group and underscores the influence of the complement pathway in the pathogenesis of this disease.
Prospective assessment of genetic effects on progression to different stages of age-related macular degeneration using multistate Markov models.
Genes in different pathways influence progression to different stages of AMD, and stage-specific therapeutic targets and more precise prediction of the development of this disease are suggested.
Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype.
The Y402H variant confers a 2-fold higher risk of late-AMD per copy in individuals of European descent and was stable to stratification by study design and AMD classification and not modified by smoking.