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Laura Lorés de Motta, Tina Schick, Lebriz Altay, Carel C B Hoyng, Anneke I Den Hollander, Sascha Fauser; The effect of genetic variants associated with age-related macular degeneration decreases in individuals aged 90 years and older. Findings from the International AMD Genomics Consortium. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4248.
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Age-related macular degeneration (AMD) is most prevalent in individuals aged 90 years and older, with a prevalence of almost 60%. A previous study suggested that genetic variants in CFH (rs1061170) and ARMS2/HTRA1 (rs10490924) confer a decreased risk in this age group (Ersoy et al., IOVS 2014; 55:1842-7), however, it was limited on sample size. In a large collaborative cohort study, we evaluated the effect of 52 AMD-associated genetic variants in individuals aged 90 years and older.
A total of 1,099 individuals of European ancestry between 90 and 102 years old were analyzed. Additionally, other age groups were included for comparison (60-69, n=721; 70-79, n=867 and 80-89, n=364). Genotypes for 52 AMD-associated genetic variants were obtained through the IAMDGC (Fritsche et al., 2016). A power calculation was carried out using the GAS Power Calculator. Association tests with AMD were performed with a Firth bias-corrected likelihood-ratio test as implemented in EPACTS. Bonferroni correction for 52 tests was applied. Genetic risk scores (GRS) were calculated based on the 52 variants, and receiver operating characteristic analysis was used to compare the discriminatory ability of the GRS in the different age groups.
In individuals aged 90 years and older, significant associations with AMD were found for rs10922109 (OR=0.51, p=5.03x10-11) and rs570618 (OR=1.72, p=7.79x10-8) in CFH, rs116503776 in C2/CFB/SKIV2L (OR=0.57, p=4.77x10-5), rs3750846 in ARMS2/HTRA1 (OR=1.76, p=3.37x10-7), and rs5754227 in SYN3/TIMP3 (OR=0.63, p=7.76x10-4). The effects of rs10922109 and rs570618 in CFH and rs3750846 in ARMS2/HTRA1 increased with age in the 60-69, 70-79 and 80-89 years age groups, but decreased in individuals aged 90 years and older. Despite >80% of power, no association was found either for rs2230199 in C3 nor for rs144629244 in C2/CFB/SKIV2L, suggesting a smaller effect of these variants in individuals aged 90 years and older. The predictive value of the GRS based on 52 variants also increased with age, but decreased in individuals aged 90 years and older.
Genetic variants have smaller effects on AMD development in individuals aged 90 years and older. These findings can be of relevance due to the increased ageing of the population and the high prevalence of AMD at old age.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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