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Nicole Restrepo, Tiana Garrett, Petra Buzkova, Richard Jensen, Barbara Klein, Ronald Klein, Tien Yin Wong, E Shyong Tai, Dana Crawford, PAGE Group; 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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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.
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.
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.
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.
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