September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The heritability of choroidal thickness in the Amish
Author Affiliations & Notes
  • Margaret A Pericak-Vance
    Univ of Miami Miller Sch of Med, Miami, Florida, United States
  • Rebecca J Sardell
    Univ of Miami Miller Sch of Med, Miami, Florida, United States
  • Muneeswar gupta Nittala
    Doheny Eye Institute, Los Angeles, California, United States
  • Larry Deon Adams
    Univ of Miami Miller Sch of Med, Miami, Florida, United States
  • Renee Laux
    Case Western Reserve University, Cleveland, Ohio, United States
  • Debra Dana
    University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • William K Scott
    Univ of Miami Miller Sch of Med, Miami, Florida, United States
  • Srinivas R Sadda
    Doheny Eye Institute, Los Angeles, California, United States
  • Dwight Stambolian
    University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Jonathan L Haines
    Case Western Reserve University, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Margaret Pericak-Vance, None; Rebecca Sardell, None; Muneeswar Nittala, None; Larry Adams, None; Renee Laux, None; Debra Dana, None; William Scott, None; Srinivas Sadda, None; Dwight Stambolian, None; Jonathan Haines, None
  • Footnotes
    Support  NIH Grant EY023164
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2644. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Margaret A Pericak-Vance, Rebecca J Sardell, Muneeswar gupta Nittala, Larry Deon Adams, Renee Laux, Debra Dana, William K Scott, Srinivas R Sadda, Dwight Stambolian, Jonathan L Haines; The heritability of choroidal thickness in the Amish. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2644.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Known genetic variants explain up to 60% of the heritability of Age-related Macular Degeneration (AMD). Unexplained heritability may partly reflect challenges defining the complex phenotype; the current classification system uses broad-scale grades that may not adequately represent the underlying biological basis of AMD. Furthermore, most studies compare advanced cases with controls. We hypothesized that parsing the AMD phenotype into heritable sub-phenotypes, each with a distinct genetic basis (“endophenotypes”), will improve prediction of risk and our understanding of the genetic architecture of AMD.

Methods : We quantified fine-scale retinal features using Ocular Coherence Tomography (OCT), compared these traits to the traditional Age-Related Eye Disease Study (AREDS) scale and assessed their potential as endophenotypes. We sampled 690 related individuals from Amish families with early/intermediate AMD cases in Pennsylvania, Ohio and Indiana. The Amish provide an excellent opportunity to analyze the heritability of complex traits given their large nuclear families and relatively homogeneous environmental and genetic backgrounds.

Results : Approximately 70% of individuals were controls (AREDS grade 0/1), 12% had early AMD (grade 2), 12% had intermediate AMD (grade 3) and 6% advanced AMD (grades 4/5). AREDS grade (rs=0.84) and choroidal thickness (r=0.82) were highly correlated between left and right eyes. Choroidal thickness was moderately correlated with AREDS grade (rs=-0.24). A generalized linear mixed model accounting for age, gender, spherical equivalent refraction, repeated measures (left and right eyes) confirmed that choroidal thickness was highly repeatable within individuals (0.78, 95% CI=0.75-0.81) and moderately heritable (additive genetic variance h2=0.40, 95% CI=0.25-0.57). Choroidal thickness also decreased with age (p<0.01, r=-0.45), and was thinner in males (p=0.04).

Conclusions : This is the first reported estimate of the heritability of choroidal thickness, highlighting a heritable, quantitative OCT trait that is measurable in all individuals and correlated with AMD severity. Moderate correlation between choroidal thickness and AREDS grade suggested that this OCT trait captures phenotypic variation not captured by the traditional AREDS system. Choroidal thickness therefore defines an AMD endophenotype useful for genetic studies aiming to further establish the genetic architecture of AMD.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

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.

×