http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12709 The curse of multiple testing has led to the adoption of a stringent Bonferroni threshold for declaring genome-wide statistical significance for any one SNP as standard practice. Although justified in avoiding false positives, this conservative approach has the potential to miss true associations as most studies are drastically underpowered. As an alternative to increasing sample size, we compare results from a typical SNP-by-SNP analysis with three other methods that incorporate regional information in order to boost or dampen an otherwise noisy signal: the haplotype method (Schaid et al. [2002] Am J Hum Genet 70:425–434), the gene-based method (Liu et al. [2010] Am J Hum Genet 87:139–145), and a new method (interaction count) that uses genome-wide screening of pairwise SNP interactions. Using a modestly sized case-control study, we conduct a genome-wide association studies (GWAS) of age-related macular degeneration, and find striking agreement across all methods in regions of known associated variants. We also find strong evidence of novel associated variants in two regions (Chromosome 2p25 and Chromosome 10p15) in which the individual SNP P-values are only suggestive, but where there are very high levels of agreement between all methods. We propose that consistency between different analysis methods may be an alternative to increasingly larger sample sizes in sifting true signals from noise in GWAS. 2013-03-26T23:21:02.109Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7993 Purpose: To examine the associations among iris, skin, or hair color, and skin sun sensitivity and the 10-year incidence of age-related maculopathy (ARM). Methods: The Blue Mountains Eye Study (BMES) recruited 3654 participants aged 49+ years at baseline (1992–1994, 82.4% participation rate). Re-examinations of 2335 participants (75.1% of survivors) were done after 5 years (1997–1999) and 1952 (76.5% of survivors) after 10 years (2002–2004). Retinal photographs were graded using the Wisconsin ARM Grading System and incident ARM confirmed using the side-by-side grading method. Iris, skin, and hair color, and sun-related skin damage were assessed and skin sun-sensitivity questions were asked at baseline. Ten-year ARM incidence was calculated using Kaplan Meier methods and discrete logistic models were used to assess associations after adjusting for age, sex, and smoking. Results: After adjustment, no significant associations were found between iris or hair color and either late- or early-incident ARM. Compared to persons with fair skin, those with very fair skin had an increased risk of developing geographic atrophy (multivariate adjusted risk ratio, RR=7.6; 95% confidence interval, CI=3.0–19.6). In contrast, compared to persons with average skin sun sensitivity, persons who reported that their skin would usually burn and tan with difficulty had a reduced risk of neovascular ARM (RR = 0.2, 95% CI = 0.0–0.7). Sun-related skin damage was not associated with late or early ARM. Conclusions: In this older cohort, we did not find a consistent pattern of association between sunlight-related factors and ARM incidence, except that persons with very fair skin might have an increased risk of geographic atrophy, consistent with our 5-year incidence data. The protective association between skin sensitivity to sun damage and neovascular ARM could have be the result of confounding by sun-avoidance behavior among persons sensitive to sunburn. 2011-06-30T04:00:06.136Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4724 Purpose: To assess the relationship between baseline dietary and supplement intakes of antioxidants and the long-term risk of incident age-related macular degeneration (AMD). Design: Australian population-based cohort study. Participants: Of 3654 baseline (1992-1994) participants initially 49 years of older, 2454 were reexamined after 5 years, 10 years, or both. Methods: Stereoscopic retinal photographs were graded using the Wisconsin Grading System. Data on potential risk factors were collected. Energy-adjusted intakes of α-carotene; β-carotene; β-cryptoxanthin; lutein and zeaxanthin; lycopene; vitamins A, C, and E; and iron and zinc were the study factors. Discrete logistic models assessed AMD risk. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated after adjusting for age, gender, smoking, and other risk factors. Main Outcome Measures: Incident early, late, and any AMD. Results: For dietary lutein and zeaxanthin, participants in the top tertile of intake had a reduced risk of incident neovascular AMD (RR, 0.35; 95% CI, 0.13-0.92), and those with above median intakes had a reduced risk of indistinct soft or reticular drusen (RR, 0.66; 95% CI, 0.48-0.92). For total zinc intake the RR comparing the top decile intake with the remaining population was 0.56 (95% CI, 0.32-0.97) for any AMD and 0.54 (95% CI, 0.30-0.97) for early AMD. The highest compared with the lowest tertile of total β-carotene intake predicted incident neovascular AMD (RR, 2.68; 95% CI, 1.03-6.96; P = 0.029, for trend). Similarly, β-carotene intake from diet alone predicted neovascular AMD (RR comparing tertile 3 with tertile 1, 2.40; 95% CI, 0.98-5.91; P = 0.027, for trend). This association was evident in both ever and never smokers. Higher intakes of total vitamin E predicted late AMD (RR compared with the lowest tertile, 2.83; 95% CI, 1.28-6.23; and RR, 2.55; 95% CI, 1.14-5.70 for the middle and highest tertiles, respectively; P = 0.22, for trend). Conclusions: In this population-based cohort study, higher dietary lutein and zeaxanthin intake reduced the risk of long-term incident AMD. This study confirmed the Age-Related Eye Disease Study finding of protective influences from zinc against AMD. Higher β-carotene intake was associated with an increased risk of AMD. 2010-04-27T05:02:46.850Z ]]>