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Predictive modeling of schizophrenia from genomic data: Comparison of polygenic risk score with kernel support vector machines approach
Authors:Timothy Vivian‐Griffiths  Emily Baker  Karl M Schmidt  Matthew Bracher‐Smith  James Walters  Andreas Artemiou  Peter Holmans  Michael C O'Donovan  Michael J Owen  Andrew Pocklington  Valentina Escott‐Price
Abstract:A major controversy in psychiatric genetics is whether nonadditive genetic interaction effects contribute to the risk of highly polygenic disorders. We applied a support vector machines (SVMs) approach, which is capable of building linear and nonlinear models using kernel methods, to classify cases from controls in a large schizophrenia case–control sample of 11,853 subjects (5,554 cases and 6,299 controls) and compared its prediction accuracy with the polygenic risk score (PRS) approach. We also investigated whether SVMs are a suitable approach to detecting nonlinear genetic effects, that is, interactions. We found that PRS provided more accurate case/control classification than either linear or nonlinear SVMs, and give a tentative explanation why PRS outperforms both multivariate regression and linear kernel SVMs. In addition, we observe that nonlinear kernel SVMs showed higher classification accuracy than linear SVMs when a large number of SNPs are entered into the model. We conclude that SVMs are a potential tool for assessing the presence of interactions, prior to searching for them explicitly.
Keywords:polygenic risk score  schizophrenia  support vector machines
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