June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Identifying endophenotypes associated with age-related macular degeneration in the Amish using OCT
Author Affiliations & Notes
  • Rebecca Sardell
    Hussman Institute for Human Genomics, University of Miami, Miami, FL
  • William Scott
    Hussman Institute for Human Genomics, University of Miami, Miami, FL
  • Larry Deon Adams
    Hussman Institute for Human Genomics, University of Miami, Miami, FL
  • Jessica Cooke Bailey
    Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH
  • Muneeswar Gupta Nittala
    Doheny Eye Institute, Los Angeles, CA
  • Srinivas R Sadda
    Doheny Eye Institute, Los Angeles, CA
  • Dwight Stambolian
    Departments of Ophthalmology and Genetics, University of Pennsylvania, Philadelphia, PA
  • Jonathan Haines
    Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH
  • Margaret A Pericak-Vance
    Hussman Institute for Human Genomics, University of Miami, Miami, FL
  • Footnotes
    Commercial Relationships Rebecca Sardell, None; William Scott, None; Larry Adams, None; Jessica Cooke Bailey, None; Muneeswar Nittala, None; Srinivas Sadda, None; Dwight Stambolian, None; Jonathan Haines, None; Margaret Pericak-Vance, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 793. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Rebecca Sardell, William Scott, Larry Deon Adams, Jessica Cooke Bailey, Muneeswar Gupta Nittala, Srinivas R Sadda, Dwight Stambolian, Jonathan Haines, Margaret A Pericak-Vance; Identifying endophenotypes associated with age-related macular degeneration in the Amish using OCT. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):793.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract 
 
Purpose
 

Several genetic and environmental risk factors of age-related macular degeneration (AMD) have been identified, yet a substantial portion of variation in disease risk and heritability remains unexplained. The unexplained variation may partly reflect challenges defining the complex phenotype. We used Ocular Coherence Tomography (OCT) to quantify fine-scale features of AMD, and assess its potential to identify endophenotypes.

 
Methods
 

We sampled 359 related individuals from 116 Amish families across Pennsylvania, Ohio and Indiana. The Amish provide an excellent opportunity to analyze the heritability of complex traits given their large nuclear families. Initially we assessed the correlation between left and right eyes, defining the phenotype using both the traditional AREDS scale and OCT traits (subfoveal choroidal thickness and drusen area in a 5mm circle). We also measured the correlation between OCT traits and AREDS grade. Finally, we quantified the heritability (h2, additive genetic variance) of OCT traits by fitting a polygenic model in SOLAR, accounting for age and gender.

 
Results
 

Approximately 41% of individuals were controls (grade 0 or 1), 33% had early AMD (grade 2), 20% had intermediate AMD (grade 3), 5% had geographic atrophy and 1% advanced neovascular AMD. AREDS grade (rs=0.77, n=312), choroidal thickness (rs=0.83, n=329) and drusen area (rs=0.73, n=346) were highly correlated between eyes. Choroidal thickness (right eyes rs=-0.33; left eyes rs=-0.37) and drusen area (right rs=0.48; left rs=0.51) were moderately correlated with AREDS grade. Choroidal thickness was significantly heritable (right: h2=0.65±SE 0.15, n=318, p<0.01; left: h2=0.50±SE 0.15, n=316, p<0.01). For individuals with drusen, drusen area was not significantly heritable (left: h2=0.11 ±SE 0.30, n=87, p=0.35; right: h2=0.20 ±SE 0.34, p=0.27, n=84), although the sample size was small.

 
Conclusions
 

Our data confirm previous findings of strong correlation between eyes for most variables, with only drusen area not showing strong heritability. However, correlation coefficients also indicated some variation in the disease process, validating the inclusion of both eyes in future analyses. Moderate correlation between OCT traits and AREDS grade, and significant heritability of choroidal thickness highlighted the value of OCT for identifying endophenotypes, and furthermore, the value of Amish populations for such analyses.

 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×