Polygenic Risk Stratification Can Predict Variability in Weight Loss After Vertical Sleeve Gastrectomy

Hou Y, Leslie D, Wang J, et al. Predicting Weight Loss After Vertical Sleeve Gastrectomy Using a Whole-Genome Sequencing–derived Polygenic Risk Score in the All of Us Cohort. Annals of Surgery. 2025;282(4):563–569.

This study used the National Institutes of Health All of Us cohort to evaluate whether a whole-genome sequencing–derived polygenic risk score (PRS) predicts postoperative weight loss after vertical sleeve gastrectomy (VSG). The analysis included more than 1,000 patients with paired genomic data and follow-up weights at 1 and 2 years postoperatively.

The PRS demonstrated a significant association with postoperative weight trajectories. At 1 year, patients in the lowest-risk quartile achieved approximately 10% greater total body weight loss compared with those in the highest-risk quartile, with the gap persisting at 2 years (average excess weight loss ~65% versus ~52%).

The PRS remained independently predictive after adjustment for baseline BMI, age, sex, and comorbidities. Model performance improved when PRS was added to clinical predictors, increasing discriminatory accuracy for identifying patients at risk of suboptimal weight loss.

These results suggest that polygenic risk stratification can meaningfully predict variability in weight loss outcomes after VSG. Integrating PRS into bariatric care could refine patient counseling, guide expectations, and identify those who may benefit from adjunctive therapies or closer follow-up.