Sofat, Reecha and Casas, Juan P. and Webster, Andrew R. and Bird, Alan C. and Mann, Samantha S. and Yates, John R. W. and Moore, Anthony T. and Sepp, Tiina and Cipriani, Valentina and Bunce, Catey and Khan, Jane C. and Shahid, Humma and Swaroop, Anand and Abecasis, Goncalo and Branham, Kari E. H. and Zareparsi, Sepideh and Bergen, Arthur A. and Klaver, Caroline C. W. and Baas, Dominique C. and Zhang, Kang and Chen, Yuhong and Gibbs, Daniel and Weber, Bernhard H. F. and Keilhauer, Claudia N. and Fritsche, Lars G. and Lotery, Andrew and Cree, Angela J. and Griffiths, Helen L. and Bhattacharya, Shomi S. and Chen, Li L. and Jenkins, Sharon A. and Peto, Tunde and Lathrop, Mark and Leveillard, Thierry and Gorin, Michael B. and Weeks, Daniel E. and Ortube, Maria Carolina and Ferrell, Robert E. and Jakobsdottir, Johanna and Conley, Yvette P. and Rahu, Mati and Seland, Johan H. and Soubrane, Gisele and Topouzis, Fotis and Vioque, Jesus and Tomazzoli, Laura and Young, Ian and Whittaker, John and Chakravarthy, Usha and de Jong, Paulus T. V. M. and Smeeth, Liam and Fletcher, Astrid and Hingorani, Aroon D. (2012) Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype. INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 41 (1). pp. 250-262. ISSN 0300-5771,
Full text not available from this repository. (Request a copy)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study designs, participant ancestry and AMD grade and to investigate effect modification by smoking, we report two unpublished genetic association studies (n = 2759) combined with data from 24 published studies (26 studies, 26 494 individuals, including 14 174 cases of AMD) of European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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FACTOR HY402H POLYMORPHISM; C-REACTIVE PROTEIN; JAPANESE POPULATION; Y402H VARIANT; HEMICENTIN-1 GENES; CIGARETTE-SMOKING; CHROMOSOME 10Q26; NO ASSOCIATION; RISK-FACTORS; CFH GENE; Age-related macular degeneration (AMD); Complement factor H gene; meta-ananlysis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 May 2020 09:21 |
| Last Modified: | 19 May 2020 09:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19272 |
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