title: Association of OCT derived drusen measurements with AMD associated-genotypic SNPs in Amish population.
abstract: OBJECTIVE
  To investigate the association of OCT derived drusen measures in Amish age-related macular degeneration (AMD) patients with known loci for macular degeneration.
  
  
  METHODS
  Members of the Old Order Amish community in Pennsylvania ages 50 and older were assessed for drusen area, volume and regions of retinal pigment epithelium (RPE) atrophy using a Cirrus High- Definition-OCT. Measurements were obtained in the macula region within a central circle (CC) of 3 mm diameter and a surrounding perifoveal ring (PR) of 3 to 5 mm diameter using the Cirrus OCT RPE analysis software. Other demographic information including age, gender and smoking status were collected. Study subjects were further genotyped to determine their risk for the AMD associated SNPs inSYN3, LIPC, ARMS2, C3, CFB, CETP, CFIandCFHgenes using TaqMan genotyping assays. The association of genotypes with OCT measures were assessed using linear trend p-values calculated from univariate and multivariate generalized linear models.
  
  
  RESULTS
  432 eyes were included in the analysis. Multivariate analysis (adjusted by age, gender and smoking status) confirmed the known significant association between AMD and macular drusen with the number of CFH risk alleles for drusen area (area increased 0.12 mm2for a risk allele increase, p<0.01), drusen volume (volume increased 0.01 mm3for a risk allele increase, p≤0.05) and area of RPE atrophy (area increased 0.43 mm2for a risk allele increase, p=0.003).SYN3risk allele G is significantly associated with larger area PR (area increased 0.09 mm2for a risk allele increase, p=0.03) and larger drusen volume in central circle (volume increased 0.01 mm3for a risk allele increase, p=0.04).
  
  
  CONCLUSIONS
  Among the genotyped SNPs tested, the CFH risk genotype appears to play a major role in determining the drusen phenotype in the Amish AMD population.
authors.affiliation: Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Venkata Ramana Murthy
authors.initials: VR
authors.lastname: Chavali
authors.affiliation: Doheny Eye Institute, Los Angeles, CA 90033 ; Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo 09920, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Diniz
authors.affiliation: Center for Preventive Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Jiayan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Center for Preventive Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Gui-Shuang
authors.initials: GS
authors.lastname: Ying
authors.affiliation: Doheny Eye Institute, Los Angeles, CA 90033 ; Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033.
authors.forename: SriniVas R
authors.initials: SR
authors.lastname: Sadda
authors.affiliation: Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Dwight
authors.initials: D
authors.lastname: Stambolian
keywords: AMD; CFH; OCT; Older Order Amish; RPE atrophy Cirrus HD-OCT; SYN3; age-related macular degeneration; drusen area; drusen volume