RT Journal Article
SR Electronic
T1 Determination of a gene and environment risk model for age-related macular degeneration
JF British Journal of Ophthalmology
JO Br J Ophthalmol
FD BMJ Publishing Group Ltd.
SP 1382
OP 1387
DO 10.1136/bjo.2010.182568
VO 94
IS 10
A1 Gibson, Jane
A1 Cree, Angela
A1 Collins, Andrew
A1 Lotery, Andrew
A1 Ennis, Sarah
YR 2010
UL http://bjo.bmj.com/content/94/10/1382.abstract
AB 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).