Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype.
Τίτλος | Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Sofat, R., Casas J. P., Webster A. R., Bird A. C., Mann S. S., Yates J. R. W., Moore A. T., Sepp T., Cipriani V., Bunce C., Khan J. C., Shahid H., Swaroop A., Abecasis G., Branham K. E. H., Zareparsi S., Bergen A. A., Klaver C. C. W., Baas D. C., Zhang K., Chen Y., Gibbs D., Weber B. H. F., Keilhauer C. N., Fritsche L. G., Lotery A., Cree A. J., Griffiths H. L., Bhattacharya S. S., Chen L. L., Jenkins S. A., Peto T., Lathrop M., Leveillard T., Gorin M. B., Weeks D. E., Ortube M. Carolina, Ferrell R. E., Jakobsdottir J., Conley Y. P., Rahu M., Seland J. H., Soubrane G., Topouzis F., Vioque J., Tomazzoli L., Young I., Whittaker J., Chakravarthy U., de Jong P. T. V. M., Smeeth L., Fletcher A., & Hingorani A. D. |
Journal | Int J Epidemiol |
Volume | 41 |
Issue | 1 |
Pagination | 250-62 |
Date Published | 2012 Feb |
ISSN | 1464-3685 |
Λέξεις κλειδιά | Aged, Aged, 80 and over, Case-Control Studies, Complement Factor H, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genotype, Humans, Macular Degeneration, Male, Polymorphism, Single Nucleotide, Prospective Studies, Smoking |
Abstract | BACKGROUND: Variation in the complement factor H gene (CFH) is associated with risk of late age-related macular degeneration (AMD). Previous studies have been case-control studies in populations of European ancestry with little differentiation in AMD subtype, and insufficient power to confirm or refute effect modification by smoking.METHODS: To precisely quantify the association of the single nucleotide polymorphism (SNP rs1061170, 'Y402H') with risk of AMD among studies with differing study designs, participant ancestry and AMD grade and to investigate effect modification by smoking, we report two unpublished genetic association studies (n = 2759) combined with data from 24 published studies (26 studies, 26,494 individuals, including 14,174 cases of AMD) of European ancestry, 10 of which provided individual-level data used to test gene-smoking interaction; and 16 published studies from non-European ancestry.RESULTS: In individuals of European ancestry, there was a significant association between Y402H and late-AMD with a per-allele odds ratio (OR) of 2.27 [95% confidence interval (CI) 2.10-2.45; P = 1.1 x 10(-161)]. There was no evidence of effect modification by smoking (P = 0.75). The frequency of Y402H varied by ancestral origin and the association with AMD in non-Europeans was less clear, limited by paucity of studies.CONCLUSION: The Y402H variant confers a 2-fold higher risk of late-AMD per copy in individuals of European descent. This was stable to stratification by study design and AMD classification and not modified by smoking. The lack of association in non-Europeans requires further verification. These findings are of direct relevance for disease prediction. New research is needed to ascertain if differences in circulating levels, expression or activity of factor H protein explain the genetic association. |
DOI | 10.1093/ije/dyr204 |
Alternate Journal | Int J Epidemiol |
PubMed ID | 22253316 |
PubMed Central ID | PMC3304526 |
Grant List | PG/09/022/26739 / / British Heart Foundation / United Kingdom EY-016862 / EY / NEI NIH HHS / United States R01 EY9859 / EY / NEI NIH HHS / United States FS/07/011 / / British Heart Foundation / United Kingdom G0601354 / / Medical Research Council / United Kingdom G0000682 / / Medical Research Council / United Kingdom 098504 / / Wellcome Trust / United Kingdom FS 05/125 / / British Heart Foundation / United Kingdom G0000067 / / Medical Research Council / United Kingdom |