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Determination of a gene and environment risk model for age-related macular degeneration
  1. Jane Gibson1,
  2. Angela Cree2,
  3. Andrew Collins1,
  4. Andrew Lotery2,3,
  5. Sarah Ennis1
  1. 1University of Southampton, Genetic Epidemiology & Bioinformatics Group, Duthie Building, Southampton General Hospital, UK
  2. 2University of Southampton, Clinical Neurosciences Division, Southampton General Hospital, UK
  3. 3Southampton Eye Unit, Southampton General Hospital, UK
  1. Correspondence to Dr S Ennis, Genetic Epidemiology & Bioinformatics Group, University of Southampton, Human Genetics Division (Mailpoint 808), Southampton General Hospital, Southampton SO16 6YD, UK; se{at}


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).

  • Age-related macular degeneration
  • association
  • risk model

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  • Funding This work was supported by the Macular Disease Society, the Macular Vision Research Foundation and the Brian Mercer Charitable Trust.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Southampton and Southwest Hants local research ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.