rs641153

Prospective cohort study of 472 elderly French participants (mean age 81.9 years) from the ALIENOR study examining incident reticular pseudodrusen (RPD). Annual incidence was 2.047% with estimated 5-year cumulative incidence of 9.73%. Risk factors identified in multivariate analysis included ARMS2 rs10490924 (HR 3.36, p=0.0009), LIPC rs10468017 (HR 2.65, p=0.0029), and thinner choroidal thickness (HR 1.06, p=0.0085). Liposoluble statin medication was protective (HR 0.18, p=0.0448).

This case-control study of 1844 unrelated white individuals examined the association between 8 SNPs in 5 genes (CFH, HTRA1/LOC387715, C2, CFB, C3) and advanced age-related macular degeneration (AMD), including geographic atrophy and choroidal neovascularization. All genetic variants showed strong associations with AMD, with odds ratios ranging from 0.44 (C2 rs9332739, protective) to 10.99 (HTRA1/LOC387715 rs10490924 TT). A combined predictive model including genetic variants and environmental factors (smoking, age, BMI) achieved 78.8% discrimination accuracy with ROC curve AUC of 0.82.

This cumulative PhD dissertation investigates genetic susceptibility factors for age-related macular degeneration (AMD). The study confirms weak associations of APOE coding variants with AMD risk (P < 0.05) but finds no association with HMCN1 variants. Large replication studies of candidate genes TLR3 and SERPING1 (1,080-4,881 cases and 2,669-2,842 controls) show no association. The authors identified 15 high-risk variants in ARMS2/HTRA1 region on chromosome 10q23.33-10qter, with the ARMS2 A69S variant showing 2.7-fold increased risk heterozygously and 8.2-fold increased risk homozygously, comparable in strength to CFH Y402H. An indel variant (c.*372_815del443ins54) in ARMS2 3' UTR causes mRNA destabilization.