You are here
Genetic determinants of age-related macular degeneration in diverse populations from the PAGE study.
Wednesday,2016-04-13 11:26 America/Los_Angeles — zdrager
| Title | Genetic determinants of age-related macular degeneration in diverse populations from the PAGE study. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Restrepo, NA, Spencer, KL, Goodloe, R, Garrett, TA, Heiss, G, Bůzková, P, Jorgensen, N, Jensen, RA, Matise, TC, Hindorff, LA, Klein, BEK, Klein, R, Wong, TY, Cheng, C-Y, Cornes, BK, Tai, E-S, Ritchie, MD, Haines, JL, Crawford, DC |
| Journal | Invest Ophthalmol Vis Sci |
| Volume | 55 |
| Issue | 10 |
| Pagination | 6839-50 |
| Date Published | 2014 Sep 9 |
| ISSN | 1552-5783 |
| Keywords | Adult, Aged, Aged, 80 and over, Complement Factor H, DNA, Ethnic Groups, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Macular Degeneration, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Prevalence, Prospective Studies, Proteins, Risk Factors, United States |
| Abstract | <p><b>PURPOSE: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1167/iovs.14-14246 |
| Alternate Journal | Invest. Ophthalmol. Vis. Sci. |
| PubMed ID | 25205864 |
| PubMed Central ID | PMC4214207 |
| Grant List | HHSN268201200036C / / PHS HHS / United States HL105756 / HL / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-15103 / HC / NHLBI NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01-HC-85239 / HC / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States T32 EY021453 / EY / NEI NIH HHS / United States U01 HG007419 / HG / NHGRI NIH HHS / United States U01HG004790 / HG / NHGRI NIH HHS / United States U01HG004798 / HG / NHGRI NIH HHS / United States U01HG004801-01 / HG / NHGRI NIH HHS / United States U01HG004802 / HG / NHGRI NIH HHS / United States U01HG004803 / HG / NHGRI NIH HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States |