Genetic Determinants of Age-Related Macular Degeneration in Diverse Populations From the PAGE Study
Year: 2014
Type: article
Study design: Observational Study
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.
Institutions: Vanderbilt University, Heidelberg University, Heidelberg University, University of North Carolina at Chapel Hill, University of Washington, Rutgers, The State University of New Jersey, National Institutes of Health, National Human Genome Research Institute, University of Wisconsin–Madison, National University of Singapore, Singapore National Eye Center, Singapore Eye Research Institute, National University Health System, Pennsylvania State University
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1023702118, G10717269, G118440752, G1220223050, G125972088, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, Epidemiology of putative genuine genetic variant: The Women's Health Intiative, G1325221871, G136105103, CHS-ULTRASOUND READING, Training Program in Quantitative Ocular Genomics, CORONARY HEART DISEASE AND STROKE, MRI READING CENTER FOR THE CARDIOVASCULAR HEALTH STUDY, G1727292203, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, Atherosclerosis Risk in Communities Study (ARIC), G215333750, G2193588257, G2194386449, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, Epidemiology of Putative Causal Variants in the Multiethnic Cohort, CCSP FIELD CENTER, G25881238, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, G270907595, G277826483, G2800149121, CENTRAL HEMOSTATIS LABORATORY FOR CCSP, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3236609591, UCLA Clinical and Translational Science Institute, G328935669, G34347772, G390162502, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G4048755144, NHGRI EpiGenVar Coordinating Center, G423252844, Atherosclerosis Risk in Communities Study (ARIC), G528395701, G5451084504, G5479317095, Atherosclerosis Risk in Communities Study (ARIC), CHARGE consortium: omics discovery for CVD and aging phenotypes, CHS Events Follow-up Study, G6203107232, G6226795708, CHS-Transition Phase, NHGRI PAGE Coordinating Center, CHS RETINAL READING CENTER, CARDIOVASCULAR HEALTH STUDY--ECHOCARDIOGRAPHY, G786153652, Genetic Epidemiology of Causal Variants Across the Life Course, G793702358, G7999488110, G812579647, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8486527673, G8593276544, Diabetes Research Center (DRC), G905887895, G936067872, Atherosclerosis Risk in Communities Study (ARIC)
OpenAlex ID: W2021466082