Abstract：
BACKGROUND: Bariatric surgery (BS) is currently the most effective long-term treatment of severe obesity. However, the interindividual variability observed in surgical outcomes suggests a moderating effect of several factors, including individual genetic background. This study aimed to investigate the contribution of the genetic architecture of body mass index (BMI) to the variability in weight loss outcomes after BS.
METHODS: A total of 106 patients with severe obesity who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy were followed up for 5 years. Changes in BMI (BMIchange) and percentage of total weight loss (%TWL) were evaluated during the postoperative period. Polygenic risk scores (PRSs), including 50 genetic variants, were calculated for each participant to determine their genetic risk of high BMI based on a previous genome-wide association study. Generalized estimating equation models were used to study the role of the individual\'s polygenic score and other factors on BMIchange and %TWL in the long term after surgery.
RESULTS: This study found an effect of the polygenic score on %TWL and BMIchange, in which patients with lower scores had better outcomes after surgery than those with higher scores. Furthermore, when analyzing only patients who underwent RYGB, the results were replicated, showing greater weight loss after surgery for patients with lower polygenic scores.
CONCLUSIONS: Our results indicate that genetic background assessed with PRSs, along with other individual factors, such as biological sex, age, and preoperative BMI, has an effect on BS outcomes and could represent a useful tool for estimating surgical outcomes in advance.
METHODS: A total of 106 patients with severe obesity who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy were followed up for 5 years. Changes in BMI (BMIchange) and percentage of total weight loss (%TWL) were evaluated during the postoperative period. Polygenic risk scores (PRSs), including 50 genetic variants, were calculated for each participant to determine their genetic risk of high BMI based on a previous genome-wide association study. Generalized estimating equation models were used to study the role of the individual\'s polygenic score and other factors on BMIchange and %TWL in the long term after surgery.
RESULTS: This study found an effect of the polygenic score on %TWL and BMIchange, in which patients with lower scores had better outcomes after surgery than those with higher scores. Furthermore, when analyzing only patients who underwent RYGB, the results were replicated, showing greater weight loss after surgery for patients with lower polygenic scores.
CONCLUSIONS: Our results indicate that genetic background assessed with PRSs, along with other individual factors, such as biological sex, age, and preoperative BMI, has an effect on BS outcomes and could represent a useful tool for estimating surgical outcomes in advance.
摘要：
背景：减肥手术是目前治疗重度肥胖最有效的长期治疗方法。然而,在手术结局中观察到的个体差异表明几个因素的调节作用，包括个体遗传背景。我们的目标是研究BMI的遗传结构对减肥手术后体重减轻结果变异性的贡献。
方法：对106例重度肥胖患者行Roux-en-Y胃旁路术或袖状胃切除术，随访5年。在术后期间评估体重指数（BMIchange）和总体重减轻百分比（％TWL）的变化。为每个参与者计算包括50个遗传变异的多基因风险评分，以根据先前的GWAS确定他们的高BMI个体遗传风险。使用广义估计方程模型来研究个体多基因得分的作用，以及其他因素,术后长期BMI变化和%TWL。
结果：我们发现多基因评分对%TWL和BMI改变有影响，其中得分较低的受试者在手术后的结局优于得分较高的受试者。此外，当仅分析接受Roux-en-Y胃旁路术的患者时，这些结果重复显示,多基因评分较低的患者术后体重减轻更大.
结论：这些结果表明，用多基因风险评分评估遗传背景，以及其他个人因素，如性别，年龄,和术前BMI,对减肥手术结局有影响,可作为提前评估手术结局的有用工具.
方法：对106例重度肥胖患者行Roux-en-Y胃旁路术或袖状胃切除术，随访5年。在术后期间评估体重指数（BMIchange）和总体重减轻百分比（％TWL）的变化。为每个参与者计算包括50个遗传变异的多基因风险评分，以根据先前的GWAS确定他们的高BMI个体遗传风险。使用广义估计方程模型来研究个体多基因得分的作用，以及其他因素,术后长期BMI变化和%TWL。
结果：我们发现多基因评分对%TWL和BMI改变有影响，其中得分较低的受试者在手术后的结局优于得分较高的受试者。此外，当仅分析接受Roux-en-Y胃旁路术的患者时，这些结果重复显示,多基因评分较低的患者术后体重减轻更大.
结论：这些结果表明，用多基因风险评分评估遗传背景，以及其他个人因素，如性别，年龄,和术前BMI,对减肥手术结局有影响,可作为提前评估手术结局的有用工具.
