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.
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