Genetics
Large AMD meta-analysis discovers two new genetic loci and confirms CETP among ten previously known susceptibility genes (Hum Mol Genet 2011)
Original title: Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration
This study performed the largest genome-wide association meta-analysis to date for advanced age-related macular degeneration (AMD), imputing 6 036 699 single-nucleotide polymorphisms in 2594 cases and 4134 controls, with follow-up replication in 5640 cases and 52 174 controls. Two new common susceptibility loci were identified: rs1999930 near FRK/COL10A1 (OR 0.87, P=1.1x10-8) and rs4711751 near VEGFA (OR 1.15, P=8.7x10-9). Alongside these novel loci, ten previously reported loci were confirmed with genome-wide significant signals, including ARMS2/HTRA1, CFH, CFB, C3, C2, CFI, LIPC, TIMP3, and CETP (rs3764261). Loci in ABCA1 and COL8A1 showed suggestive evidence of association. The authors conclude the novel variants implicate angiogenesis and extracellular collagen matrix pathways in advanced AMD.
Original abstract
Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date for advanced AMD. We imputed 6 036 699 single-nucleotide polymorphisms with the 1000 Genomes Project reference genotypes on 2594 cases and 4134 controls with follow-up replication of top signals in 5640 cases and 52 174 controls. We identified two new common susceptibility alleles, rs1999930 on 6q21-q22.3 near FRK/COL10A1 [odds ratio (OR) 0.87; P = 1.1 × 10(-8)] and rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 × 10(-9)). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genome-wide significant signals in this large study. Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD. The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.