rs10490924

rs10490924 is a single nucleotide polymorphism located in the ARMS2 gene on chromosome 10q26, within the ARMS2/HTRA1 region. The variant corresponds to the A69S amino acid substitution in the ARMS2 protein, a change from alanine to serine at residue 69. It is one of the most studied genetic variants in the region due to its strong association with age-related macular degeneration (AMD).

Association with AMD is well established. In numerous genome-wide association studies across diverse populations, rs10490924 shows a robust link to increased AMD risk. The effect size varies by study and ancestry, but the risk allele is consistently associated with higher odds of developing AMD, including both the neovascular (wet) form and geographic atrophy. The precise causal mechanism remains a topic of investigation, as the risk signal in this region is in strong linkage disequilibrium with variants in nearby genes, particularly HTRA1, making it difficult to pinpoint a single functional variant.

Genetic and population considerations are important. The ARMS2/HTRA1 locus is a major contributor to AMD susceptibility, but the exact contribution of rs10490924 versus neighboring variants is not fully resolved. Allele frequencies and the strength of association can differ among populations, reflecting diverse genetic backgrounds. rs10490924 is often included in SNP panels and polygenic risk scores for AMD research and is sometimes used as a reference point in discussing the region’s broader genetic architecture.

Overall, rs10490924 serves as a key marker in the genetics of AMD, illustrating how variants in the ARMS2/HTRA1 interval contribute to disease risk and prompting ongoing studies into the underlying biological mechanisms.