Background/Aims There are limited data from India on genetic variants influencing late age-related macular degeneration (AMD). We have previously reported associations from a population-based study in India (the India age-related eye disease study (INDEYE)) of early AMD and single nucleotide polymorphisms (SNPs) in ARMS2/HTRA1 and no association with CFH, C2 or CFB. Late AMD cases were too few for meaningful analyses. We aimed to investigate SNPs for late AMD through case enrichment and extend the loci for early AMD.
Methods Fundus images of late AMD hospital cases were independently graded by the modified Wisconsin AMD grading scheme. In total 510 cases with late AMD (14 geographic atrophy and 496 neovascular AMD (nvAMD)), 1876 with early AMD and 1176 with no signs of AMD underwent genotyping for selected SNPs. We investigated genotype and per-allele additive associations (OR and 95% CIs) with nvAMD or early AMD. Bonferroni adjusted P values are presented.
Results We found associations with nvAMD for CFHY402H variant (rs1061170) (OR=1.99, 95% CI 1.67 to 2.37, P=10−6), ARMS2 (rs10490924) (OR=2.94, 95% CI 2.45 to 3.52, P=10−9), C2 (rs547154) (OR=0.67, 95% CI 0.53 to 0.85, P=0.01), ABCA1 (rs1883025) (OR=0.77, 95% CI 0.65 to 0.92, P=0.04) and an SNP near VEGFA (rs4711751) (OR=0.64, 95% CI 0.54 to 0.77, P=10−3). We found no associations of TLR3 (rs3775291), CFD (rs3826945), FRK (rs1999930) or LIPC (rs10468017) or APOE ε4 alleles with nvAMD or early AMD, nor between early AMD and rs1883025 or rs4711751.
Conclusions The major genetic determinants of nvAMD risk in India are similar to those in other ancestries, while findings for early AMD suggest potential differences in the pathophysiology of AMD development.
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Contributors AEF had full access to all the data in the study and takes full responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: AEF, RDR, UC, LS, DN. Acquisition, analysis or interpretation of data: all authors. Drafting of the manuscript: AEF, RDR. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: AEF. Obtained funding: AEF, UC, RDR, DN, LS. Administrative, technical or material support: RDR, UC, PS, AEF. Study supervision: RDR, AEF.
Funding Wellcome Trust UK Grants G073300 and G082571.
Competing interests None declared.
Ethics approval Ethics approval was received from the Indian Council for Medical Research, the Research Ethics Committees of All India Institute of Medical Sciences (AIIMS) Delhi, Aravind Eye Hospital Pondicherry (Tamil Nadu), Aravind Eye Hospital Madurai (Tamil Nadu), the London School of Hygiene & Tropical Medicine, and Queen’s University Belfast.
Provenance and peer review Not commissioned; externally peer reviewed.
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