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Genetic Risk Score Increased Discriminant Efficiency of Predictive Models for Type 2 Diabetes Mellitus Using Machine Learning: Cohort Study.

ABSTRACT: Background: Previous studies have constructed prediction models for type 2 diabetes mellitus (T2DM), but machine learning was rarely used and few focused on genetic prediction. This study aimed to establish an effective T2DM prediction tool and to further explore the potential of genetic risk scores (GRS) via various classifiers among rural adults. Methods: In this prospective study, the GRS for a total of 5,712 participants from the Henan Rural Cohort Study was calculated. Cox proportional hazards (CPH) regression was used to analyze the associations between GRS and T2DM. CPH, artificial neural network (ANN), random forest (RF), and gradient boosting machine (GBM) were used to establish prediction models, respectively. The area under the receiver operating characteristic curve (AUC) and net reclassification index (NRI) were used to assess the discrimination ability of the models. The decision curve was plotted to determine the clinical-utility for prediction models. Results: Compared with the individuals in the lowest quintile of the GRS, the HR (95% CI) was 2.06 (1.40 to 3.03) for those with the highest quintile of GRS (P _trend < 0.05). Based on conventional predictors, the AUCs of the prediction model were 0.815, 0.816, 0.843, and 0.851 via CPH, ANN, RF, and GBM, respectively. Changes with the integration of GRS for CPH, ANN, RF, and GBM were 0.001, 0.002, 0.018, and 0.033, respectively. The reclassifications were significantly improved for all classifiers when adding GRS (NRI: 41.2% for CPH; 41.0% for ANN; 46.4% for ANN; 45.1% for GBM). Decision curve analysis indicated the clinical benefits of model combined GRS. Conclusion: The prediction model combined with GRS may provide incremental predictions of performance beyond conventional factors for T2DM, which demonstrated the potential clinical use of genetic markers to screen vulnerable populations. Clinical Trial Registration: The Henan Rural Cohort Study is registered in the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). http://www.chictr.org.cn/showproj.aspx?proj=11375.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7925839 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Diabetes Mellitus is an increasingly prevalent chronic disease characterized by the body's inability to metabolize glucose. The objective of this study was to build an effective predictive model with high sensitivity and selectivity to better identify Canadian patients at risk of having Diabetes Mellitus based on patient demographic data and the laboratory results during their visits to medical facilities. METHODS:Using the most recent records of 13,309 Canadian patients aged between 18 and 90 years, along with their laboratory information (age, sex, fasting blood glucose, body mass index, high-density lipoprotein, triglycerides, blood pressure, and low-density lipoprotein), we built predictive models using Logistic Regression and Gradient Boosting Machine (GBM) techniques. The area under the receiver operating characteristic curve (AROC) was used to evaluate the discriminatory capability of these models. We used the adjusted threshold method and the class weight method to improve sensitivity - the proportion of Diabetes Mellitus patients correctly predicted by the model. We also compared these models to other learning machine techniques such as Decision Tree and Random Forest. RESULTS:The AROC for the proposed GBM model is 84.7% with a sensitivity of 71.6% and the AROC for the proposed Logistic Regression model is 84.0% with a sensitivity of 73.4%. The GBM and Logistic Regression models perform better than the Random Forest and Decision Tree models. CONCLUSIONS:The ability of our model to predict patients with Diabetes using some commonly used lab results is high with satisfactory sensitivity. These models can be built into an online computer program to help physicians in predicting patients with future occurrence of diabetes and providing necessary preventive interventions. The model is developed and validated on the Canadian population which is more specific and powerful to apply on Canadian patients than existing models developed from US or other populations. Fasting blood glucose, body mass index, high-density lipoprotein, and triglycerides were the most important predictors in these models.

Project description:Background:Statistically derived cardiovascular risk calculators (CVRC) that use conventional risk factors, generally underestimate or overestimate the risk of cardiovascular disease (CVD) or stroke events primarily due to lack of integration of plaque burden. This study investigates the role of machine learning (ML)-based CVD/stroke risk calculators (CVRCML) and compares against statistically derived CVRC (CVRCStat) based on (I) conventional factors or (II) combined conventional with plaque burden (integrated factors). Methods:The proposed study is divided into 3 parts: (I) statistical calculator: initially, the 10-year CVD/stroke risk was computed using 13 types of CVRCStat (without and with plaque burden) and binary risk stratification of the patients was performed using the predefined thresholds and risk classes; (II) ML calculator: using the same risk factors (without and with plaque burden), as adopted in 13 different CVRCStat, the patients were again risk-stratified using CVRCML based on support vector machine (SVM) and finally; (III) both types of calculators were evaluated using AUC based on ROC analysis, which was computed using combination of predicted class and endpoint equivalent to CVD/stroke events. Results:An Institutional Review Board approved 202 patients (156 males and 46 females) of Japanese ethnicity were recruited for this study with a mean age of 69±11 years. The AUC for 13 different types of CVRCStat calculators were: AECRS2.0 (AUC 0.83, P<0.001), QRISK3 (AUC 0.72, P<0.001), WHO (AUC 0.70, P<0.001), ASCVD (AUC 0.67, P<0.001), FRScardio (AUC 0.67, P<0.01), FRSstroke (AUC 0.64, P<0.001), MSRC (AUC 0.63, P=0.03), UKPDS56 (AUC 0.63, P<0.001), NIPPON (AUC 0.63, P<0.001), PROCAM (AUC 0.59, P<0.001), RRS (AUC 0.57, P<0.001), UKPDS60 (AUC 0.53, P<0.001), and SCORE (AUC 0.45, P<0.001), while the AUC for the CVRCML with integrated risk factors (AUC 0.88, P<0.001), a 42% increase in performance. The overall risk-stratification accuracy for the CVRCML with integrated risk factors was 92.52% which was higher compared all the other CVRCStat. Conclusions:ML-based CVD/stroke risk calculator provided a higher predictive ability of 10-year CVD/stroke compared to the 13 different types of statistically derived risk calculators including integrated model AECRS 2.0.

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Genetic Risk Score Increased Discriminant Efficiency of Predictive Models for Type 2 Diabetes Mellitus Using Machine Learning: Cohort Study.

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