多基因风险评分预测减重手术后的体重减轻情况。
Polygenic risk score for predicting weight loss after bariatric surgery.
机构信息
Institute of Nutrition and Functional Foods (INAF) and.
School of Nutrition, Université Laval, Quebec City, Quebec, Canada.
出版信息
JCI Insight. 2018 Sep 6;3(17). doi: 10.1172/jci.insight.122011.
BACKGROUND
The extent of weight loss among patients undergoing bariatric surgery is highly variable. Herein, we tested the contribution of genetic background to such interindividual variability after biliopancreatic diversion with duodenal switch.
METHODS
Percentage of excess body weight loss (%EBWL) was monitored in 865 patients over a period of 48 months after bariatric surgery, and two polygenic risk scores were constructed with 186 and 11 (PRS186 and PRS11) single nucleotide polymorphisms previously associated with body mass index (BMI).
RESULTS
The accuracy of the %EBWL logistic prediction model - including initial BMI, age, sex, and surgery modality, and assessed as the area under the receiver operating characteristics (ROC) curve adjusted for optimism (AUCadj = 0.867) - significantly increased after the inclusion of PRS186 (ΔAUCadj = 0.021; 95% CI of the difference [95% CIdiff] = 0.005-0.038) but not PRS11 (ΔAUCadj= 0.008; 95% CIdiff= -0.003-0.019). The overall fit of the longitudinal linear mixed model for %EBWL showed a significant increase after addition of PRS186 (-2 log-likelihood = 12.3; P = 0.002) and PRS11 (-2 log-likelihood = 9.9; P = 0.007). A significant interaction with postsurgery time was found for PRS186 (β = -0.003; P = 0.008) and PRS11 (β = -0.008; P = 0.03). The inclusion of PRS186 and PRS11 in the model improved the cost-effectiveness of bariatric surgery by reducing the percentage of false negatives from 20.4% to 10.9% and 10.2%, respectively.
CONCLUSION
These results revealed that genetic background has a significant impact on weight loss after biliopancreatic diversion with duodenal switch. Likewise, the improvement in weight loss prediction after addition of polygenic risk scores is cost-effective, suggesting that genetic testing could potentially be used in the presurgical assessment of patients with severe obesity.
FUNDING
Heart and Stroke Foundation of Canada (G-17-0016627) and Canada Research Chair in Genomics Applied to Nutrition and Metabolic Health (no. 950-231-580).
背景
接受减重手术的患者的减重程度存在很大差异。在此，我们测试了遗传背景对胆胰分流十二指肠转位术后个体间这种差异的影响。
方法
在接受减重手术后的 48 个月期间，监测了 865 例患者的超重体重减轻百分比（%EBWL），并使用与体重指数（BMI）相关的 186 个和 11 个（PRS186 和 PRS11）单核苷酸多态性构建了两个多基因风险评分。
结果
包括初始 BMI、年龄、性别和手术方式在内的%EBWL 逻辑预测模型的准确性 - 作为接收者操作特征（ROC）曲线下面积的调整（AUCadj=0.867）来评估预测的准确性，在纳入 PRS186 后显著增加（ΔAUCadj=0.021；差异的 95%置信区间[95% CIdiff]=0.005-0.038），但纳入 PRS11 后则没有（ΔAUCadj=0.008；95% CIdiff=-0.003-0.019）。%EBWL 的纵向线性混合模型的总体拟合度在加入 PRS186（-2 对数似然=12.3；P=0.002）和 PRS11（-2 对数似然=9.9；P=0.007）后显著增加。发现 PRS186（β=-0.003；P=0.008）和 PRS11（β=-0.008；P=0.03）与术后时间存在显著的交互作用。纳入 PRS186 和 PRS11 可使模型的成本效益提高，使假阴性率从 20.4%分别降低到 10.9%和 10.2%。
结论
这些结果表明，遗传背景对胆胰分流十二指肠转位术后的体重减轻有显著影响。同样，加入多基因风险评分后对体重减轻的预测改善是具有成本效益的，这表明基因检测可能在严重肥胖患者的术前评估中得到应用。
资金
加拿大心脏和中风基金会（G-17-0016627）和加拿大营养与代谢健康应用基因组学研究主席（编号 950-231-580）。
Zotero 插件