Nicole A Restrepo1, Kylee L Spencer2, Robert Goodloe1, Tiana A Garrett3, Gerardo Heiss3, Petra Bůžková4, Neal Jorgensen4, Richard A Jensen5, Tara C Matise6, Lucia A Hindorff7, Barbara E K Klein8, Ronald Klein8, Tien Y Wong9, Ching-Yu Cheng10, Belinda K Cornes10, E-Shyong Tai11, Marylyn D Ritchie12, Jonathan L Haines1, Dana C Crawford13. 1. Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States. 2. Department of Biology and Environmental Science, Heidelberg University, Tiffin, Ohio, United States. 3. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States. 4. Department of Biostatistics, University of Washington, Seattle, Washington, United States. 5. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States. 6. Department of Genetics, Rutgers University, Piscataway, New Jersey, United States. 7. Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States. 8. Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States. 9. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore. 10. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. 11. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. 12. Center for Systems Genomics, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, United States. 13. Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States.
Abstract
PURPOSE: Substantial progress has been made in identifying susceptibility variants for 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 single nucleotide polymorphism (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. 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: Index variants of AMD, rs1061170 (CFH) and rs10490924 (ARMS2), were associated with AMD at P=3.05×10(-8) and P=6.36×10(-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 at an uncorrected P value<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 (P<0.05), but these associations did not survive strict corrections for multiple testing. 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. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
RCT Entities:
PURPOSE: Substantial progress has been made in identifying susceptibility variants for 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 single nucleotide polymorphism (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. 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: Index variants of AMD, rs1061170 (CFH) and rs10490924 (ARMS2), were associated with AMD at P=3.05×10(-8) and P=6.36×10(-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 at an uncorrected P value<0.05. Four lipid-associated SNPS (LPLrs328, TRIB1rs6987702, CETPrs1800775, and KCTD10/MVKrs2338104) were associated with AMD in African Americans and Mexican Americans (P<0.05), but these associations did not survive strict corrections for multiple testing. 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. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
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