Article

Population differences in genetic risk for age-related macular degeneration and implications for genetic testing.

Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
Archives of ophthalmology (Impact Factor: 4.49). 01/2012; 130(1):116-7. DOI: 10.1001/archopthalmol.2011.1370
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    ABSTRACT: Purpose:Substantial progress has been made in identifying susceptibility variants for age-related macular degeneration (AMD) in European populations; however, few studies have been conducted to understand the role these variants play in AMD risk in diverse populations. The present study aims to examine AMD risk across diverse populations in known and suspected AMD complement factor and lipid-related loci. Methods:Targeted genotyping was performed across study sites for AMD and lipid trait-associated SNPs. Genetic association tests were performed at individual sites and then meta-analyzed using logistic regression assuming an additive genetic model stratified by self-described race/ethnicity to determine risk of any AMD. Participants included cases with early or late AMD and controls with no signs of AMD as determined by fundus photography. Populations included in this study were European Americans, African Americans, Mexican Americans, and Singaporeans from the Population Architecture using Genomics and Epidemiology (PAGE) study. Results:AMD index variants rs1061170 (CFH) and rs10490924 (ARMS2) were associated with AMD at p=3.05x10-8 and p=6.36x10-6, respectively, in European Americans. In general, none of the major AMD index variants generalized to our non-European populations with the exception of rs10490924 in Mexican Americans (p<0.05). Four lipid-associated SNPs (LPL rs328, TRIB1 rs6987702, CETP rs1800775, and KCTD10/MVK rs2338104) were associated with AMD in African Americans and Mexican Americans at a liberal significance threshold (p<0.05). Conclusions:While most associations did not generalize in the non-European populations, variants within lipid-related genes were found to be associated with AMD. This study highlights the need for larger well-powered studies in non-European populations.
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    Expert Review of Ophthalmology 04/2013; 8(2):127-140. DOI:10.1586/eop.13.3

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