Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype
| Autor: | Arthur A.B. Bergen, Sharon Jenkins, Gisèle Soubrane, Ian S. Young, Daniel E. Weeks, Caroline C W Klaver, Mati Rahu, Aroon D. Hingorani, Andrew J. Lotery, Paulus T. V. M. de Jong, Li L Chen, Bernhard H. F. Weber, Maria Carolina Ortube, Andrew R. Webster, Johanna Jakobsdottir, Humma Shahid, Thierry Léveillard, Juan P. Casas, Gonçalo R. Abecasis, Johan H. Seland, Usha Chakravarthy, Fotis Topouzis, Astrid E. Fletcher, Helen Griffiths, Yuhong Chen, Lars G. Fritsche, Kari Branham, Reecha Sofat, T. Sepp, Kang Zhang, Jane C. Khan, Catey Bunce, Jesús Vioque, Samantha Mann, Angela J. Cree, Sepideh Zareparsi, Claudia N. Keilhauer, Robert E. Ferrell, John C. Whittaker, Michael B. Gorin, John R.W. Yates, Yvette P. Conley, Alan C. Bird, Shomi S. Bhattacharya, Anand Swaroop, Mark Lathrop, Laura Tomazzoli, Valentina Cipriani, Dominique C Baas, Daniel Gibbs, Liam Smeeth, Anthony T. Moore, Tunde Peto |
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| Přispěvatelé: | ANS - Amsterdam Neuroscience, Human Genetics, Ophthalmology, Epidemiology, Netherlands Institute for Neuroscience (NIN) |
| Rok vydání: | 2012 |
| Předmět: |
Oncology
Male medicine.medical_specialty genetic structures Genotype Epidemiology Single-nucleotide polymorphism Polymorphism Single Nucleotide White People Macular Degeneration Internal medicine medicine SNP Humans Genetic Predisposition to Disease Prospective Studies Allele Genetic association Aged Aged 80 and over business.industry Smoking Case-control study General Medicine Odds ratio eye diseases Factor H Meta-analysis Case-Control Studies Complement Factor H Female sense organs business Genetic and Intergenerational Epidemiology |
| Zdroj: | International journal of epidemiology, 41(1), 250-262. Oxford University Press International Journal of Epidemiology, 41(1), 250-262. Oxford University Press International Journal of Epidemiology, 41, 250-262. Oxford University Press |
| ISSN: | 1464-3685 0300-5771 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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