June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Genetic determinants of Age-related Macular Degeneration in Diverse Populations: the Population Architecture using Genomics and Epidemiology (PAGE) Study
Author Affiliations & Notes
  • Nicole Restrepo
    Center for Human Genetics Research, Vanderbilt University, Nashville, TN
  • Tiana Garrett
    Department of Epidemiology, University of North Carolina, Chapel Hill, Chapel Hill, NC
  • Petra Buzkova
    Department of Biostatistics, University of Washington, Seattle, WA
  • Richard Jensen
    Department of Biostatistics, University of Washington, Seattle, WA
  • Barbara Klein
    Office of Population Genomics, National Human Genome Research Institute, Bethesda, MD
  • Ronald Klein
    Office of Population Genomics, National Human Genome Research Institute, Bethesda, MD
  • Tien Yin Wong
    Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI
  • E Shyong Tai
    Singapore Eye Research Institute, Singapore national Eye Centre, Singapore, Singapore
  • Dana Crawford
    Center for Human Genetics Research, Vanderbilt University, Nashville, TN
  • Footnotes
    Commercial Relationships Nicole Restrepo, None; Tiana Garrett, None; Petra Buzkova, None; Richard Jensen, None; Barbara Klein, None; Ronald Klein, None; Tien Yin Wong, Allergan (C), Bayer (C), Novartis (C), Pfizer (C), GSK (F), Roche (F); E Shyong Tai, None; Dana Crawford, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 6168. doi:
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    • Get Citation

      Nicole Restrepo, Tiana Garrett, Petra Buzkova, Richard Jensen, Barbara Klein, Ronald Klein, Tien Yin Wong, E Shyong Tai, Dana Crawford, ; Genetic determinants of Age-related Macular Degeneration in Diverse Populations: the Population Architecture using Genomics and Epidemiology (PAGE) Study. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6168.

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

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Abstract
 
Purpose
 

Substantial progress has been made in identifying susceptibility variants for AMD. The most widely replicated loci are Complement Factor H (CFH) Y402H and Age-related Maculopathy Susceptibility-2 (ARMS2),which were discovered in European populations. To date, little data exist for these variants in diverse populations. A major goal of the Population Architecture using Genomics and Epidemiology (PAGE) study is to describe the underlying genetic architecture of common, complex diseases such as AMD across diverse populations.

 
Methods
 

The PAGE study consists of the National Health and Nutrition Examination Surveys, Atherosclerosis Risk in Communities Study,and the Cardiovascular Health Study. Included are the Singapore Prospective Study Programme and Singapore Malay Eye Study. Targeted genotyping was performed for AMD-associated SNPs in CFH, CFI, ARMS2, VEGF,and lipid trait loci. AMD cases were >60 years and presented with early/late AMD, determined by fundus photography. A total of 830, 95, 107,and 21 cases and 5,710, 1,172, 863,and 206 controls from European Americans, African Americans, Malays, and Chinese, respectively, were available for study. We performed a meta-analysis following logistic regression assuming an additive genetic model performed at each study site and adjusted for age, sex, body mass index, smoking status,and HDL.

 
Results
 

In European Americans, rs1061170 (CFH) and rs10490924 (ARMS2) replicated at p=3.7x10-10 (OR= 1.61, 95% CI= 1.85and 1.41) and p=1.8x10-5 (OR = 1.49, 95% CI=1.78 and 1.25), respectively. None of the CFH or ARMS2 SNPs tested generalized to African Americans (p>0.05). Interestingly, the HDL associated variant CETP rs1800775 (OR=0.55; 95% CI=0.86 and 0.35; p=0.009) was associated with AMD in African Americans but not European Americans or Chinese suggesting a potential risk modifier in lipid pathways to AMD in this population.

 
Conclusions
 

Further studies are needed to determine if lack of generalization in major CFH and ARMS2 variants is due to statistical power or differences in linkage disequilibrium and allelic distribution across these diverse populations.

 
 
Synthesis view plot of meta-analysis results. P- values transformed by -log10, with the threshold (p = 0.05) marked by a red line. Arrows show direction of effect (beta). P-values, beta’s, and coded allele frequencies plotted by race/ethnicity.
 
Synthesis view plot of meta-analysis results. P- values transformed by -log10, with the threshold (p = 0.05) marked by a red line. Arrows show direction of effect (beta). P-values, beta’s, and coded allele frequencies plotted by race/ethnicity.
 
Keywords: 412 age-related macular degeneration • 539 genetics  
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