Determination of a gene and environment risk model for age related macular degeneration.

Jane Gibson (1) , Angela J Cree (1) , Andrew Collins (1) , Andrew Lotery (1) , Sarah Ennis (1)

1 University of Southampton

Background/aims: Recently we identified association between age related macular degeneration (AMD) and 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, gender and smoking). Individual risk scores were assessed between groups of cases and controls. Results: In the SERPING1 region rs2511989 remains most significantly associated (p=1.77E-05, odds ratio of 0.67). One haplotype, containing the rs2511989 variant and the majority of SERPING1, exhibits marginally stronger association (p=5.13E-06, odds ratio of 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=1.65E-50) with a combined population attributable risk (PAR) 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=9.81E-71) and across AREDS stratified cases (p=1.88E-11).

Mots clés: Macula; Genetics

Jane Gibson, Angela J Cree, Andrew Collins, Andrew Lotery, Sarah Ennis. Determination of a gene and environment risk model for age related macular degeneration.. British Journal of Ophthalmology, 2010, 94 (10), pp.1382. ⟨10.1136/bjo.2010.182568⟩. ⟨hal-00557364⟩