Key result
A body mass index polygenic score was associated with percentage total weight loss at 12 months (indirect effect p=0.018) and HDL-cholesterol at 6 months (p=0.004) following bariatric surgery.
Why the study?
Metabolic and bariatric surgery is effective for severe obesity, but individual responses vary widely, partly due to genetic predisposition.
Is a body mass index polygenic score associated with weight loss and lipid outcomes after metabolic and bariatric surgery?
Cohort (n=225)
Is a body mass index polygenic score associated with weight loss and lipid outcomes after metabolic and bariatric surgery?
p-value: p=0.018
A BMI polygenic score is associated with weight loss and lipid changes after metabolic and bariatric surgery, suggesting potential utility in personalized obesity treatment.
PGS may stratify MBS responses; hypothesis-generating and should not yet guide practice.
Metabolic and bariatric surgery (MBS) is an effective treatment for severe obesity, though individual responses vary widely, partly due to genetic predisposition. This study investigates the association of a body mass index (BMI) polygenic score (PGS) with weight loss and metabolic outcomes following surgery. A cohort of 225 patients undergoing MBS was analyzed at baseline (T0), six (T6), and twelve (T12) months, with anthropometric and biochemical parameters recorded at each time point. Total weight loss (TWL) and excess weight loss (EWL) percentages were calculated. PGS was computed using the LDpred-grid Bayesian method. The mean age was 45.9 ± 9.4 years. Males had a higher baseline prevalence of type 2 diabetes (T2D) and comorbidities (p < 0.001). Linear regression analysis confirmed an association between PGS and baseline BMI (p = 0.012). Moreover, mediation analysis revealed that baseline BMI mediated the effect of the PGS on %TWL at T12, with an indirect effect (p-value = 0.018). In contrast, high-density lipoprotein-cholesterol (HDL-C) at T6 and triglycerides (TG) at T12 showed direct associations with the PGS (p-value = 0.004 and p-value = 0.08, respectively), with no significant mediation by BMI. This study showed a BMI-mediated association of PGS with %TWL and a direct association with lipid changes, suggesting its potential integration into personalized obesity treatment.
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Aldegheri et al. (2025) conducted a cohort in Severe obesity (n=225). Body mass index (BMI) polygenic score (PGS) was evaluated on Percentage total weight loss (%TWL) at 12 months (p=0.018). A body mass index polygenic score was associated with percentage total weight loss at 12 months (indirect effect p=0.018) and HDL-cholesterol at 6 months (p=0.004) following bariatric surgery.
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