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bioRxiv · 10.1101/2022.08.22.504882

A machine learning model for disease risk prediction by integrating genetic and non-genetic factors

Xu, Y.·Wang, C.·Li, Z.·Cai, Y.·Young, O.·Lyu, A.·Zhang, L.
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Abstract

Polygenic risk score (PRS) has been widely used to identify the high-risk individuals from the general population, which would be helpful for disease prevention and early treatment. Many methods have been developed to calculate PRS by weighted aggregating the phenotype-associated risk alleles from genome-wide association studies. However, only considering genetic effects may not be sufficient for risk prediction because the disease risk is not only related to genetic factors but also non-genetic factors, e.g., diet, physical exercise et al. But it is still a challenge to integrate these genetic and non-genetic factors into a unified machine learning framework for disease risk prediction. In this paper, we proposed PRSIMD (PRS Integrating Multi-source Data), a machine learning model that applies posterior regularization to integrate genetic and non-genetic factors to improve disease risk prediction. Also, we applied Mendelian Randomization analysis to identify the causal non-genetic risk factors for the selected diseases. We applied PRSIMD to predict type 2 diabetes and coronary artery disease from UK Biobank and observed that PRSIMD was significantly better than the methods to calculate PRS including p-value threshold (P+T), PRSice2, SBLUP, DMSLMM, and LDpred2. In addition, we observed that PRSIMD achieved the better predictive power than the composite risk score.

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Xu, Y., Wang, C., Li, Z., Cai, Y., Young, O., Lyu, A., Zhang, L.. 2022-08-23. A machine learning model for disease risk prediction by integrating genetic and non-genetic factors. https://doi.org/10.1101/2022.08.22.504882

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