Comparing the XGBoost machine learning algorithm to polygenic scoring for the prediction of intelligence based on genotype data

Abstract

AbstractA polygenic score (PGS) is a linear combination of effects from a GWAS that represents and can be used to predict genetic predisposition to a particular phenotype. A key limitation of the PGS method is that it assumes additive and independent SNP effects, when it is known that epistasis (gene interactions) can contribute to complex traits. Machine learning methods can potentially overcome this limitation by virtue of their ability to capture nonlinear interactions in high dimensional data. Intelligence is a complex trait for which PGS prediction currently explains up to 5.2% of the variance, a relatively small proportion of the heritability estimate of 50% obtained from twin studies. Here, we use gradient boosting, a machine learning technique based on an ensemble of weak prediction models, to predict intelligence from genotype data. We found that while gradient boosting did not outperform the PGS method in predicting intelligence based on SNP data, it was capable of achieving similar predictive performance with less than a quarter of the SNPs with the top SNPs identified as being important for predictive performance being biologically meaningful. These results indicate that ML methods may be useful in interpreting the biological meaning underpinning SNP-phenotype associations due to the smaller number of SNPs required in the ML model as opposed to the standard PGS method based on GWAS.