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Agnostic polygenic prediction of weight loss after bariatric surgery
Bastien Vallée Marcotte, Juan de Toro-Martín, André Tchernof, Louis Pérusse, Simon Marceau, Marie-Claude Vohl
Bastien Vallée Marcotte, Juan de Toro-Martín, André Tchernof, Louis Pérusse, Simon Marceau, Marie-Claude Vohl
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Research Article Gastroenterology Genetics Metabolism

Agnostic polygenic prediction of weight loss after bariatric surgery

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Abstract

A large interindividual variability in weight loss outcomes following bariatric surgery is reported. To ensure optimal management of patients, it is crucial to accurately identify candidates most likely to benefit the most from the intervention. Since genetic variants largely contribute to surgery response, polygenic scores (PGS) derived from genome-wide association studies (GWAS) could constitute valuable tools for clinical decision making. We developed and evaluated PGS to predict the weight loss response in 540 patients with a body mass index (BMI) of 35 kg/m2 or higher who underwent biliopancreatic diversion with duodenal switch. Summary statistics derived from BMI-derived GWAS, together with summary statistics from previously published GWAS of BMI and adiposity features, were used to construct, evaluate, and benchmark weight loss PGS. The full-adjusted BMI PGS model built in the entire cohort explained 39.6% of the mean-over-time excessive body weight loss (%EBWL), while the BMI-PGS built in the training dataset explained 38.9%. All benchmarked PGS based on BMI showed a significant relationship with mean-over-time %EBWL. These findings highlight the potential of BMI PGS in predicting weight loss after bariatric surgery and support their use as promising tools to improve the effectiveness of future antiobesity treatments.

Authors

Bastien Vallée Marcotte, Juan de Toro-Martín, André Tchernof, Louis Pérusse, Simon Marceau, Marie-Claude Vohl

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Figure 5

Predictive capacity of polygenic risk scores (PGS) to classify participants according to their excess body weight loss (%EBWL).

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Predictive capacity of polygenic risk scores (PGS) to classify participa...
Left panels show the distribution of mean-over-time %EBWL (mean %EBWL) across quintiles of each PGS, while right panels display the proportion of participants classified into %EBWL response subgroups (low, average, and high) within each PGS quintile category. (A and B) PGSTRAIN. (C and D) PGSBMI. (E and F) PGSLOCKE. (G and H) PGSKHERA. Box-and-whisker plots represent the median and interquartile range, with individual data points overlaid. Stacked bar plots illustrate the percentage of participants within each %EBWL response subgroup. Fisher’s exact test P values assessed differences in response distribution across PGS quintiles.

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