Patients with low polygenic risk scores lost 28.4% total weight versus 22.3% in high PRS patients 5 years post-bariatric surgery, highlighting genetic impact.
Does a lower polygenic risk score predict improved long-term weight loss outcomes in patients with severe obesity undergoing bariatric surgery?
Polygenic risk scores can identify patients likely to achieve greater long-term weight loss following bariatric surgery, highlighting the role of genetics in personalizing obesity treatment.
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The global obesity epidemic has reached alarming levels, affecting over 1 billion people worldwide1. The chance of developing a number of health issues, including type 2 diabetes, cardiovascular disease, and hypertension, is greatly increased by this condition2. While conservative treatments, including lifestyle modifications and pharmacotherapies, have been used to manage obesity, they often fall short in delivering sustainable long-term outcomes3,4. In cases of severe obesity, bariatric surgery, such as sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), has proven to be the most successful option, providing significant and long-lasting weight loss. Even if these treatments are successful, there is a significant amount of variation in each individual’s weight loss results, indicating that genetic predisposition is a significant factor in determining whether bariatric surgery is helpful in the long run. A recent study investigated the impact of polygenic risk scores (PRS) on weight loss outcomes after bariatric surgery over a 5-year follow-up period5. The study included 106 patients with severe obesity who underwent RYGB or SG, evaluating changes in body mass index (BMI) and percentage of total weight loss (%TWL) postoperatively. Patients with a lower PRS for BMI experienced significantly greater weight loss after surgery than those with higher PRS scores. Specifically, patients with low PRS achieved an average %TWL of 28.4% after 5 years, while those with high PRS had an average %TWL of only 22.3%. These results underscore the potential of PRS as a valuable tool for identifying patients who may experience substantial weight loss following bariatric surgery, emphasizing the importance of genetic factors in predicting long-term outcomes. The influence of genetic factors on weight-loss outcomes following bariatric surgery has gained increasing attention. Numerous studies have shown that the degree of weight loss and chance of weight gain following surgery are highly influenced by an individual’s genetic history, as determined by polygenic risk scores5,6. PRS allows researchers to quantify an individual’s genetic predisposition to obesity and their responsiveness to weight loss therapies. It is the cumulative effect of several genetic variations associated with variables related to obesity, such as BMI, waist-to-hip ratio, and adiposity7. In the context of bariatric surgery, PRS can help identify patients with a higher likelihood of achieving successful outcomes. When clinical factors including age, surgery type, and comorbidities are combined with PRS, the prediction of weight loss response after surgery is greatly enhanced8,9. Healthcare professionals can now customize treatment programs based on a patient’s genetic predisposition, improve weight loss outcomes, and lower the possibility of less-than-ideal outcomes, thanks to its integration into preoperative examinations. Genetic variations between individuals are partially responsible for the variation in weight loss outcomes following various bariatric surgeries such as RYGB and SG. Patients undergoing RYGB who have lower PRS scores typically lose more weight than those with higher scores, indicating that RYGB may be more beneficial for people who have lower genetic susceptibility to obesity5,10. This finding underscores the importance of considering PRS when selecting the most appropriate surgical intervention. Other research has indicated that the type of bariatric surgery modulates the impact of genetic factors on weight loss outcomes11. Certain genetic variants in genes associated with obesity are linked to more substantial weight loss after RYGB compared to SG12. These findings highlight the potential for personalized surgical approaches that take into account an individual’s genetic makeup, potentially leading to improved long-term weight loss success. Apart from genetic considerations, there are multiple variables that affect the result of weight loss after bariatric surgery. Preoperative BMI, sex, age, and the existence of comorbidities like diabetes mellitus all have a substantial influence on weight loss after surgery13. Younger patients tend to experience greater weight loss than older individuals, likely due to differences in metabolic capacity and energy requirements14,15. Moreover, women generally have better weight loss outcomes compared to men, with hormonal factors and metabolic differences playing a role in this disparity16. The preoperative BMI is another important factor in determining the result of weight loss; after surgery, those with a higher preoperative BMI have a greater reduction in BMI17. When compared to patients with lower baseline weights, and patients with higher baseline weights typically lose a smaller percentage of their total body weight, so this does not always convert to a larger percentage of total weight reduction. The integration of polygenic risk scores into the preoperative assessment of patients undergoing bariatric surgery has the potential to revolutionize the field of obesity treatment. By identifying individuals who are more likely to benefit from specific bariatric procedures, healthcare providers can develop personalized treatment plans that maximize weight-loss outcomes and improve long-term success. Additionally, incorporating PRS into clinical decision making could reduce the likelihood of suboptimal results and the need for revision surgery, ultimately improving the cost-effectiveness of bariatric interventions. Future research should focus on refining the accuracy of the PRS by incorporating a broader range of genetic variants associated with obesity and weight loss outcomes. As genome-wide association studies (GWAS) continue to identify new obesity-related genes, the predictive power of PRS is expected to improve, making it a valuable tool in the development of precision medicine for obesity treatment. Furthermore, research examining the interplay between genetic, environmental, and lifestyle factors will offer a more thorough understanding of the factors influencing weight loss success following bariatric surgery, facilitating the creation of more efficient and customized interventions. In conclusion, polygenic risk scores play a significant role in predicting weight-loss outcomes after bariatric surgery. By incorporating the PRS into preoperative assessments, clinicians can identify patients who are more likely to benefit from specific surgical procedures and enhance the success rates of bariatric interventions. As the field of precision medicine continues to evolve, the integration of genetic data into clinical decision-making holds promise for improving the management of obesity and achieving sustainable long-term weight loss outcomes in patients undergoing bariatric surgery.
Roy et al. (Thu,) reported a other. Patients with low polygenic risk scores lost 28.4% total weight versus 22.3% in high PRS patients 5 years post-bariatric surgery, highlighting genetic impact.