Evaluation of Machine Learning and Traditional Statistical Models to Assess the Value of Stroke Genetic Liability for Prediction of Risk of Stroke Within the UK Biobank

<b>Background and Objective:</b> Stroke is one of the leading causes of mortality and long-term disability in adults over 18 years of age globally, and its increasing incidence has become a global public health concern. Accurate stroke prediction is highly valuable for early intervention and treatment. There is a scarcity of studies evaluating the prediction value of genetic liability in the prediction of the risk of stroke. <b>Materials and Methods:</b> Our study involved 243,339 participants of European ancestry from the UK Biobank. We created stroke genetic liability using data from MEGASTROKE genome-wide association studies (GWASs). In our study, we built four predictive models with and without stroke genetic liability in the training set, namely a Cox proportional hazard (Coxph) model, gradient boosting model (GBM), decision tree (DT), and random forest (RF), to estimate time-to-event risk for stroke. We then assessed their performances in the testing set. <b>Results:</b> Each unit (standard deviation) increase in genetic liability increases the risk of incident stroke by 7% (HR = 1.07, 95% CI = 1.02, 1.12, <i>p</i>-value = 0.0030). The risk of stroke was greater in the higher genetic liability group, demonstrated by a 14% increased risk (HR = 1.14, 95% CI = 1.02, 1.27, <i>p</i>-value = 0.02) compared with the low genetic liability group. The Coxph model including genetic liability was the best-performing model for stroke prediction achieving an AUC of 69.54 (95% CI = 67.40, 71.68), NRI of 0.202 (95% CI = 0.12, 0.28; <i>p</i>-value = 0.000) and IDI of 1.0 × 10^-4 (95% CI = 0.000, 3.0 × 10^-4; <i>p</i>-value = 0.13) compared with the Cox model without genetic liability. <b>Conclusions:</b> Incorporating genetic liability in prediction models slightly improved prediction models of stroke beyond conventional risk factors.