Purpose: There is still a debate as to whether the LOC387715 or HTRA1 genes represent the key significant association identified with age-related macular degeneration (AMD) on the long arm of chromosome 10, region 26.
Methods: An Australian patient cohort was genotyped by using tagged single nucleotide polymorphisms (tSNPs) to identify a causal SNP within this region.
Results: Multiple tSNPs across the region showed association with AMD with the tSNP rs3793917 (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.36-5.05, P = 2.8 × 10(-13)) having the highest association with AMD. This tSNP occurred in the intergenic region between the LOC387715 and HTRA1 genes. A second tSNP rs2672587 (OR, 2.92; 95% CI, 2.04-4.17; P = 7.7 × 10(-11)) located in intron 1 of the HTRA1 gene had the second highest association with AMD. After logistic regression analysis, the only tSNP to survive covariate testing was rs3793917, which occurred in the same LD block as the HTRA1 promoter SNP rs11200638 (r(2) = 0.88, D' = 0.97).
Conclusions: The findings indicate that the intergenic region between the tSNP rs3793917 and the SNP rs11200638 in the HTRA1 gene is the most likely site explaining the significant association with AMD.