PRS Model Reveals Impact of Genetic and Lifestyle on DR Risk

The researchers found it noteworthy that individuals with high genetic risk but also had a healthy lifestyle had standardized DR rates comparable to or even lower than those with low genetic risk but an unhealthy lifestyle. Photo: Steven Ferrucci, OD. Click image to enlarge. A great deal of evidence supports the protective role against diabetic retinopathy (DR) of a healthy lifestyle. As a key modifiable risk factor, lifestyle is directly relevant to public health intervention recommendations from doctors and policymakers. Using data from two long-term, prospective cohorts of distinct ethnicities in the UK and China, a study published this Monday in Ophthalmology has provided evidence supporting both the independent and joint associations of genetic risk and lifestyle with the risk of developing DR. Participants with high genetic risk and an unfavorable lifestyle had more than double the risk of developing DR compared to those with low genetic risk and a favorable lifestyle. No significant interaction effect was observed between genetic risk and lifestyle; nevertheless, adherence to a favorable lifestyle was associated with a reduced risk of DR regardless of genetic risk.This multicenter, multiethnic cohort study included 91,691 participants with DR-free prediabetes/diabetes from the UK Biobank, as well as 1,119 participants with DR-free diabetes from the Guangzhou Diabetic Eye Study for independent validation. A machine learning-driven polygenic risk score (PRS) for DR was constructed by integrating 182 literature-derived single nucleotide polymorphisms, which was subsequently applied to the two multiethnic, prospective cohorts. Lifestyle adherence was determined using a scoring system based on four behavioral factors (abstinence from smoking, optimal weight control, regular physical activity and healthy sleep) and was categorized as favorable (presence of three to four factors), intermediate (two factors) and unfavorable (zero or one factor).The study determined that participants at high genetic risk had a 37% higher risk of developing incident DR than those at low genetic risk, regardless of lifestyle (hazard ratio; HR: 1.37). An unfavorable lifestyle was associated with a 49% higher risk than a favorable lifestyle, regardless of genetic risk (HR: 1.49). High genetic risk combined with an unfavorable lifestyle more than doubled the DR risk (HR: 2.09). Among participants at high genetic risk, a favorable lifestyle was associated with a 44% lower DR risk (HR: 0.56), corresponding to a reduction in the standardized DR rates from 7.5% to 4.6%.“A key challenge in integrating genetic risk into clinical practice is ensuring effective communication between healthcare providers and the public, as concerns have been raised that knowledge of genetic risk can be misinterpreted as deterministic and demotivate behavior change,” the study authors wrote in their paper. “However, our results provide evidence that lifestyle modifications powerfully mitigate risk regardless of their genetic predisposition.”These results emphasize the need for multifactorial strategies that promote healthy behavioral changes for all individuals with prediabetes and diabetes, regardless of their genetic predisposition.Click here for the journal source. Yang S, Xin Z, Liu B, et al. Decoding gene–lifestyle synergy in diabetic retinopathy development: a transethnic prospective cohort study. Ophthalmology. April 27, 2026. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.