| Determination of a gene and environment risk model for age-related macular degeneration. | |
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MedLine Citation:
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PMID: 20576771 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: We have recently identified an association between age-related macular degeneration (AMD) and genetic variants in the serpin peptidase inhibitor, clade G, member 1 (SERPING1) gene. In the current study we interrogated the genomic region in linkage disequilibrium (LD) with the SERPING1 gene, and modelled the contribution to disease of known genetic and environmental AMD risk factors. METHODS: We analysed genes neighbouring SERPING1 and examined haplotype association with AMD. A stepwise logistic regression model was developed including known genetic and environmental risk factors (age, sex and smoking). Individual risk scores were assessed between groups of cases and controls. RESULTS: In SERPING1 region rs2511989 remains most significantly associated (p=1.77×10(-5), OR 0.67). One haplotype, containing the rs2511989 variant and the majority of SERPING1, exhibits marginally stronger association (p=5.13×10(-6), OR 0.66). Our risk model includes six SNPs in CFH, C3, HTRA1 and SERPING1, showing independent effects, which together account for 45% of risk of developing AMD (p=1.65×10(-50)) with a combined population attributable risk of 87%. CONCLUSION: Results implicate SERPING1, with no convincing evidence for involvement of other genes in the region. We demonstrate a multifactorial model with significant differences in risk scores for cases versus controls (p=9.81×10(-71)) and across Age-Related Eye Disease Study (AREDS) score-stratified cases (p=1.88×10(-11)). |
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Authors:
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Jane Gibson; Angela Cree; Andrew Collins; Andrew Lotery; Sarah Ennis |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-24 |
Journal Detail:
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Title: The British journal of ophthalmology Volume: 94 ISSN: 1468-2079 ISO Abbreviation: Br J Ophthalmol Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-07 Completed Date: 2010-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0421041 Medline TA: Br J Ophthalmol Country: England |
Other Details:
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Languages: eng Pagination: 1382-7 Citation Subset: IM |
Affiliation:
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Genetic Epidemiology & Bioinformatics Group, University of Southampton, Human Genetics Division, Southampton General Hospital, Southampton, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Area Under Curve Chromosomes, Human, Pair 11 / genetics* Complement C1 Inactivator Proteins / genetics* Environment* Female Genotype Haplotypes Humans Linkage Disequilibrium Logistic Models Macular Degeneration Male Polymorphism, Single Nucleotide / genetics* Risk Factors |
| Chemical | |
Reg. No./Substance:
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0/Complement C1 Inactivator Proteins; 0/SERPING1 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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