Lead Researcher: Professor Paul Baird
CERA’s Ocular Genetics Research focuses predominantly on genetic studies of age-related macular degeneration (AMD) and refractive error to establish how genetic changes are involved in these diseases. We have a patient database of more than 30,000 patient samples in which to undertake our genetic studies as well as a large amount of epidemiological data that enables us to look at how genes interact with our environment. The aim of our research is to translate our findings into improved patient care, to slow progression of disease or prevent disease onset with the ultimate aim of personalising treatment.
Family linkage analysis
- Myopia linkage analysis – three large families collected as part of the Genes in Myopia (GEM) study were genotyped; the largest containing 35 people with 18 affected with myopia. Genotyping is a process where a patient’s DNA is mapped and every gene is recorded.
Linkage analysis followed by fine mapping has allowed us to narrow the myopia gene-containing region to 0.8cM (~ 800,000 base pairs) on chromosome 2 in these families. Identification of the causative genetic variant in these families is being undertaken.
- Linkage analysis in AMD families – sixty-five AMD families have undergone whole genome linkage analysis. A number of linkage signals are being followed up in a larger collection of AMD families.
- We have reported association of single nucleotide polymorphisms (SNPs) in the hepatocyte growth factor (HGF) with myopia and these findings have been replicated in an Asian population as well as a US Caucasian population. This is the first gene to be replicated in myopia in different ethnicities. In addition, we have also reported the association of this gene with hypermetropia, the first time that a gene has been implicated in this type of refractive error. Studies to explore how this gene influences refraction are being undertaken.
- Risk assessment chip – this study involves the development of a risk assessment chip. This is being accomplished through standardisation of Indian and Australian AMD patient repositories, identification of a common molecular signature (haplotypes) for the complement (and other known AMD risk genes) and correlate these with clinical phenotype and progression. Genome-wide association study data has been obtained from both Australian and Indian case and control samples to allow detection of genetic variants.
- Progression of AMD and disease subtypes – this study aims to characterise the rate of AMD disease progression from intermediate and dry (geographic atrophy) disease to late stage disease through assessment of a number of AMD risk genes, age of disease onset and rate of disease progression. We will also undertake studies in subtypes of AMD.
- Pharmacogenomics and predictors of outcome in response to Anti-VEGF (ranibizumab or Lucentis). Genotyping of known AMD risk genes is being undertaken as well as other clinical factors to assess the impact that they have on treatment outcome in AMD patients.
Genome wide studies
- Genome wide association studies are being undertaken to allow detection of genetic variants, quantitative trait loci as well as copy number changes on the population based Blue Mountains Eye Study (BMES) and in our GEM twin cohort.
- Genome wide expression studies aim to assess their impact on disease. This is being undertaken in identical twins who are discordant for a number of different measures.
Analysis of gene environmental factors
AMD and obesity – over 20,000 individuals from the Health 2000 population-based study are being analysed to explore the influence of five different measures of obesity on AMD. The cohort is being assessed and genotyping in over 25 genes is currently underway to establish how genes and obesity are involved in this disease.