title: Heritability of Choroidal Thickness in the Amish.
abstract: To evaluate the heritability of choroidal thickness and its relationship to age-related macular degeneration (AMD).
  
  
  
  Cohort study.
  
  
  
  Six hundred eighty-nine individuals from Amish families with early or intermediate AMD.
  
  
  
  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.
  
  
  
  Heritability of choroidal thickness and its phenotypic and genetic correlation with the AMD phenotype (CARMS category).
  
  
  
  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).
  
  
  
  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.
authors: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
authors: Rebecca J
authors: RJ
authors: Sardell
authors: Department of Ophthalmology, Doheny Eye Institute, University of California, Los Angeles, Los Angeles, California.
authors: Muneeswar G
authors: MG
authors: Nittala
authors: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
authors: Larry D
authors: LD
authors: Adams
authors: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
authors: Reneé A
authors: RA
authors: Laux
authors: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
authors: Jessica N
authors: JN
authors: Cooke Bailey
authors: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
authors: Denise
authors: D
authors: Fuzzell
authors: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
authors: Sarada
authors: S
authors: Fuzzell
authors: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
authors: Lori
authors: L
authors: Reinhart-Mercer
authors: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
authors: Laura J
authors: LJ
authors: Caywood
authors: Departments of Ophthalmology and Genetics, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Violet
authors: V
authors: Horst
authors: Departments of Ophthalmology and Genetics, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Tine
authors: T
authors: Mackay
authors: Departments of Ophthalmology and Genetics, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Debbie
authors: D
authors: Dana
authors: Department of Ophthalmology, Doheny Eye Institute, University of California, Los Angeles, Los Angeles, California.
authors: SriniVas R
authors: SR
authors: Sadda
authors: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
authors: William K
authors: WK
authors: Scott
authors: Departments of Ophthalmology and Genetics, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Dwight
authors: D
authors: Stambolian
authors: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
authors: Jonathan L
authors: JL
authors: Haines
authors: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida. Electronic address: mpericak@med.miami.edu.
authors: Margaret A
authors: MA
authors: Pericak-Vance
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061365:Amish / Q000235:genetics*; D002829:Choroid / Q000000981:diagnostic imaging / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000235:genetics; D019655:Quantitative Trait, Heritable; D041623:Tomography, Optical Coherence