A study recently investigated the genetic distribution of age-related macular degeneration (AMD)–associated risks to determine the influence of lifestyle on genetic outcomes. The researchers found that genetic risk variants contribute to late AMD in most cases, particularly when the age-related maculopathy susceptibility 2 (ARMS2) gene and complement pathway are involved.

After assessing the 17,174 study subjects with AMD, the team reported that the risk variants with the greatest differences between late AMD cases and controls were located in the ARMS2 and complement factor H genes, “the most prominent genetic pathways contributing to late AMD,” the researchers wrote in their paper. Late cases with genetic risk variants in three different pathways were the most common (35%), and 89% of late cases had a positive total genetic risk score. Genetic risk scores increased with AMD severity.

Additionally, lifestyle was a strong determinant of outcome for each genetic risk category. “Unfavorable lifestyles increased the risk of late AMD at least twofold,” the team noted. “This highlights the possibility of counteracting predicted disease outcome with lifestyle.”

The study authors concluded that genetic risks associated with AMD are highly prevalent and that risk variants in the complement pathway are the most significant drivers of late cases. However, “AMD is mostly the result of multiple genetic pathways and lifestyle,” they suggest. They recommended future research and intervention be tailored to different pathways.

Colijn JM, Meester M, Verzijden T, et al. Genetic risk, lifestyle and AMD in Europe: the EYE-RISK consortium. Ophthalmology. November 27, 2020. [Epub ahead of print].