GWAS of age-related macular degeneration reveals two new loci implying shared genetic components with central serous chorioretinopathy.

PURPOSE: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population.

DESIGN: Genome-wide association study (GWAS).

SUBJECTS: A total of 3,772 AMD cases and 16,770 controls in the Japanese population were enrolled in the association analyses.

METHODS: We conducted a meta-analysis of two independent GWASs that included a total of 2,663 AMD cases and 9,471 controls using the imputation reference panel for genotype imputation specified for the Japanese population (N = 3,541). A replication study was performed employing an independent set of 1,109 AMD cases and 7,299 controls.

MAIN OUTCOME MEASURE: Associations of genetic variants with AMD.

RESULTS: A meta-analysis of the two GWASs identified six loci significantly associated with AMD (P < 5.0 × 10-8 ). Of these loci, four were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2); two were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all data sets, we observed strong associations in these loci (Pmeta = 1.88 × 10-12 and 1.35 × 10-9 , for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were significantly associated with CSC (P = 4.86 × 10-3 and 4.28 × 10-3 , for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci, and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg = -0.33, P = 0.01, false discovery rate = 0.099).

CONCLUSION: Our findings imply shared genetic components conferring the risk of both AMD and CSC.