Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10−22). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l−1 (P=5.82 × 10−21) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10−18), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10−11) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10−8). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

ABSTRACT.Purpose: To determine the distribution of choroidal thickness (CT) and ocular factors associated with CT in high myopic eyes in comparison with emmetropic eyes of young healthy adults. Methods: A case-control study of 648 young, male subjects, including 520 high myopes and 128 emmetropes. Choroidal imaging was performed using enhanced depth imaging spectral domain optical coherence tomography. Images were postprocessed using adaptive compensation for quality enhancement. CT was measured at nine locations, including subfovea and 1.5 and 3 mm nasal, temporal, superior and inferior to fovea. Results: The CT at the subfovea was significantly thinner (mean AE standard error: 225.87 AE 5.51 lm) for high myopes compared to emmetropes (375.15 AE 6.58 lm, p < 0.001). Likewise, CT in high myopic group was significantly thinner than emmetropic control group at all locations (p for trend <0.001 for all locations). Distribution of CT showed a markedly different pattern in high myopic eyes (thickest superiorly at 3 mm, 265.97 AE 5.97 lm) and emmetropic eyes (thickest subfoveally, 375.15 AE 6.58 lm). Choroid was thinnest at nasal 3 mm location in both the myopic (108.85 AE 3.97 lm) and emmetropic (238.25 AE 6.72 lm) groups. Among the ocular factors studied, axial length, posterior staphyloma and chorioretinal atrophy were the significant predictors of CT. Conclusions: Highly myopic eyes have significantly thinner choroid and showed different distribution pattern, compared to emmetropes. Axial length, posterior staphyloma and chorio-retinal atrophy are the strongest determinants of CT.