Centre for Eye Research Australia (CERA) - Research Publications
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ItemNo Preview AvailableGenetic Loci for Retinal Arteriolar Microcirculation(PUBLIC LIBRARY SCIENCE, 2013-06-12)Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10(-8). This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.
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ItemNo Preview AvailableShort Sleep Duration Is Associated with Risk of Future Diabetes but Not Cardiovascular Disease: a Prospective Study and Meta-Analysis(PUBLIC LIBRARY SCIENCE, 2013-11-25)Genetic factors explain a majority of risk variance for age-related macular degeneration (AMD). While genome-wide association studies (GWAS) for late AMD implicate genes in complement, inflammatory and lipid pathways, the genetic architecture of early AMD has been relatively under studied. We conducted a GWAS meta-analysis of early AMD, including 4,089 individuals with prevalent signs of early AMD (soft drusen and/or retinal pigment epithelial changes) and 20,453 individuals without these signs. For various published late AMD risk loci, we also compared effect sizes between early and late AMD using an additional 484 individuals with prevalent late AMD. GWAS meta-analysis confirmed previously reported association of variants at the complement factor H (CFH) (peak P = 1.5×10(-31)) and age-related maculopathy susceptibility 2 (ARMS2) (P = 4.3×10(-24)) loci, and suggested Apolipoprotein E (ApoE) polymorphisms (rs2075650; P = 1.1×10(-6)) associated with early AMD. Other possible loci that did not reach GWAS significance included variants in the zinc finger protein gene GLI3 (rs2049622; P = 8.9×10(-6)) and upstream of GLI2 (rs6721654; P = 6.5×10(-6)), encoding retinal Sonic hedgehog signalling regulators, and in the tyrosinase (TYR) gene (rs621313; P = 3.5×10(-6)), involved in melanin biosynthesis. For a range of published, late AMD risk loci, estimated effect sizes were significantly lower for early than late AMD. This study confirms the involvement of multiple established AMD risk variants in early AMD, but suggests weaker genetic effects on the risk of early AMD relative to late AMD. Several biological processes were suggested to be potentially specific for early AMD, including pathways regulating RPE cell melanin content and signalling pathways potentially involved in retinal regeneration, generating hypotheses for further investigation.
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ItemFactors Associated with Knowledge of Diabetes in Patients with Type 2 Diabetes Using the Diabetes Knowledge Test Validated with Rasch Analysis(PUBLIC LIBRARY SCIENCE, 2013-12-03)OBJECTIVE: In patients with Type 2 diabetes, to determine the factors associated with diabetes knowledge, derived from Rasch analysis, and compare results with a traditional raw scoring method. RESEARCH DESIGN & METHODS: Participants in this cross-sectional study underwent a comprehensive clinical and biochemical assessment. Diabetes knowledge (main outcome) was assessed using the Diabetes Knowledge Test (DKT) which was psychometrically validated using Rasch analysis. The relationship between diabetes knowledge and risk factors identified during univariate analyses was examined using multivariable linear regression. The results using raw and Rasch-transformed methods were descriptively compared. RESULTS: 181 patients (mean age±standard deviation = 66.97±9.17 years; 113 (62%) male) were included. Using Rasch-derived DKT scores, those with greater education (β = 1.14; CI: 0.25,2.04, p = 0.013); had seen an ophthalmologist (β = 1.65; CI: 0.63,2.66, p = 0.002), and spoke English at home (β = 1.37; CI: 0.43,2.31, p = 0.005) had significantly better diabetes knowledge than those with less education, had not seen an ophthalmologist and spoke a language other than English, respectively. Patients who were members of the National Diabetes Service Scheme (NDSS) and had seen a diabetes educator also had better diabetes knowledge than their counterparts. Higher HbA1c level was independently associated with worse diabetes knowledge. Using raw measures, access to an ophthalmologist and NDSS membership were not independently associated with diabetes knowledge. CONCLUSIONS: Sociodemographic, clinical and service use factors were independently associated with diabetes knowledge based on both raw scores and Rasch-derived scores, which supports the implementation of targeted interventions to improve patients' knowledge. Choice of psychometric analytical method can affect study outcomes and should be considered during intervention development.