Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Dec;123(12):2537-2544.
doi: 10.1016/j.ophtha.2016.09.001. Epub 2016 Oct 19.

Heritability of Choroidal Thickness in the Amish

Rebecca J Sardell  1 , Muneeswar G Nittala  2 , Larry D Adams  1 , Reneé A Laux  3 , Jessica N Cooke Bailey  3 , Denise Fuzzell  3 , Sarada Fuzzell  3 , Lori Reinhart-Mercer  1 , Laura J Caywood  1 , Violet Horst  4 , Tine Mackay  4 , Debbie Dana  4 , SriniVas R Sadda  2 , William K Scott  1 , Dwight Stambolian  4 , Jonathan L Haines  3 , Margaret A Pericak-Vance  5
Affiliations

Heritability of Choroidal Thickness in the Amish

Rebecca J Sardell et al. Ophthalmology. 2016 Dec.

Abstract

Purpose: To evaluate the heritability of choroidal thickness and its relationship to age-related macular degeneration (AMD).

Design: Cohort study.

Participants: Six hundred eighty-nine individuals from Amish families with early or intermediate AMD.

Methods: Ocular coherence tomography was used to quantify choroidal thickness, and fundus photography was used to classify eyes into categories using a modified Clinical Age-Related Maculopathy Staging (CARMS) system. Repeatability and heritability of choroidal thickness and its phenotypic and genetic correlations with the AMD phenotype (CARMS category) were estimated using a generalized linear mixed model (GLMM) approach that accounted for relatedness, repeated measures (left and right eyes), and the effects of age, gender, and refraction.

Main outcome measures: Heritability of choroidal thickness and its phenotypic and genetic correlation with the AMD phenotype (CARMS category).

Results: Phenotypic correlation between choroidal thickness and CARMS category was moderate (Spearman's rank correlation, rs = -0.24; n = 1313 eyes) and significant (GLMM posterior mean, -4.27; 95% credible interval [CI], -7.88 to -0.79; P = 0.02) after controlling for relatedness, age, gender, and refraction. Eyes with advanced AMD had thinner choroids than eyes without AMD (posterior mean, -73.8; 95% CI, -94.7 to -54.6; P < 0.001; n = 1178 eyes). Choroidal thickness was highly repeatable within individuals (repeatability, 0.78; 95% CI, 0.68 to 0.89) and moderately heritable (heritability, 0.40; 95% CI, 0.14 to 0.51), but did not show significant genetic correlation with CARMS category, although the effect size was moderate (genetic correlation, -0.18; 95% CI, -0.49 to 0.16). Choroidal thickness also varied with age, gender, and refraction. The CARMS category showed moderate heritability (heritability, 0.49; 95% CI, 0.26 to 0.72).

Conclusions: We quantify the heritability of choroidal thickness for the first time, highlighting a heritable, quantitative trait that is measurable in all individuals regardless of AMD affection status, and moderately phenotypically correlated with AMD severity. Choroidal thickness therefore may capture variation not captured by the CARMS system. However, because the genetic correlation between choroidal thickness and AMD severity was not significant in our data set, genes associated with the 2 traits may not overlap substantially. Future studies should therefore test for genetic variation associated with choroidal thickness to determine the overlap in genetic basis with AMD.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: No conflicting relationship exists for any author.

Figures

Figure 1
Figure 1
Distribution of subfoveal choroidal thickness in microns for A) right eyes and B) left eyes.
Figure 2
Figure 2
Phenotypic correlation of A) CARMS category and B) subfoveal choroidal thickness between left and right eyes, and correlation between subfoveal choroidal thickness and CARMS category for C) right eyes, and D) left eyes. Points have been jittered for visualization.
Figure 3
Figure 3
Correlation between A) CARMS category and age, and B) subfoveal choroidal thickness and age. Points are jittered for visualization.
See this image and copyright information in PMC

References

    1. Congdon N, O’Colmain B, Klaver CC, et al. Causes and prevalence of visual impairment among adults in the united states. Arch Ophthalmol. 2004;122:477–85. - PubMed
    1. Naj AC, Scott WK, Courtenay MD, et al. Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis. Ann Hum Genet. 2013;77:215–31. - PMC - PubMed
    1. Klein R, Peto T, Bird A, et al. The epidemiology of age-related macular degeneration. Am J Ophthalmol. 2004;137:486–95. - PubMed
    1. Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-related eye disease study report number 3. Ophthalmology. 2000;107:2224–32. - PMC - PubMed
    1. Seddon JM, Cote J, Page WF, et al. The US twin study of age-related macular degeneration: Relative roles of genetic and environmental influences. Arch Ophthalmol. 2005;123:321–7. - PubMed

Publication types