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ItemCan genetic associations change with age? CFH and age-related macular degenerationAdams, MKM ; Simpson, JA ; Richardson, AJ ; Guymer, RH ; Williamson, E ; Cantsilieris, S ; English, DR ; Aung, KZ ; Makeyeva, GA ; Giles, GG ; Hopper, J ; Robman, LD ; Baird, PN (OXFORD UNIV PRESS, 2012-12-01)Genetic variation in the gene encoding complement factor H (CFH) on chromosome 1q31 has repeatedly been associated with an increased risk of age-related macular degeneration (AMD); however, previous studies have had inadequate numbers of participants across a sufficiently wide age range to determine whether the association varies by age. We conducted a genetic case-control study using data from 2294 cases and 2294 controls selected from the Melbourne Collaborative Cohort Study, matched on age, sex and region of origin. Four consistently replicated CFH single-nucleotide polymorphisms (SNPs) were genotyped: rs1061170 (Y402H), rs2274700, rs393955 and rs800292; their relationship with AMD prevalence was determined across the age range 48-86. A difference in genotype frequencies was seen across age groups, where the low-risk homozygote prevalence rose with each increasing age group. Associations with early AMD were strongly modified by age for three of the four SNPs (interaction P-value: 0.01-0.00003). An inverse association between the high-risk homozygote for each SNP and early AMD was observed in the younger age groups [odds ratios (OR) range 0.37-0.48 for age <55], reversing to a positive association with increasing age (OR 1.87-2.8 for age >75). The direction of associations for this gene change was from inverse to risk with increasing age. These findings have important implications for predictive models for AMD and potentially other age-related diseases which extrapolate risks from older cohorts, as they assume homogeneity of association by age, which might not exist.
ItemNo Preview Available20/20-Alcohol and Age-related Macular Degeneration: The Melbourne Collaborative Cohort StudyAdams, MKM ; Chong, EW ; Williamson, E ; Aung, KZ ; Makeyeva, GA ; Giles, GG ; English, DR ; Hopper, J ; Guymer, RH ; Baird, PN ; Robman, LD ; Simpson, JA (OXFORD UNIV PRESS INC, 2012-08-15)Little evidence exists regarding associations between age-related macular degeneration (AMD) and moderate alcohol consumption, patterns of consumption, or different types of alcoholic beverage. The authors examined associations between AMD prevalence and alcohol intake using 20,963 participants from the Melbourne Collaborative Cohort Study aged 40-69 years at baseline (1990-1994). Participants' alcohol consumption was determined from a structured interview at baseline. At follow-up from 2003 to 2007, digital macula photographs of both eyes were taken and evaluated for early and late AMD signs. Drinking more than 20 g of alcohol per day was associated with an approximate 20% increase in the odds of early AMD (odds ratio = 1.21, 95% confidence interval: 1.06, 1.38; P = 0.004) when compared with those who reported no alcohol intake at baseline, having adjusted for sex, age, smoking, country of birth, education, physical activity, and energy from food. This positive association was apparent for wine, beer, and spirits. The estimates were similar for both sexes. The odds ratio for those drinking more than 20 g of alcohol per day for late AMD was 1.44 (95% confidence interval: 0.85, 2.45; P = 0.17). These results show a modest association between alcohol consumption and increased AMD risk.