Deep learning-based identification of genetic variants: Application to Alzheimer's disease classification
Deep learning is a promising tool that uses nonlinear transformations to extract features from high-dimensional data. Although deep learning has been used in several genetic studies, it is challenging in genome-wide association studies (GWAS) with high-dimensional genomic data. Here we propose a novel three-step approach for identification of genetic variants using deep learning to identify phenotype-related single nucleotide polymorphisms (SNPs) and develop accurate classification models. In the first step, we divided the whole genome into non-overlapping fragments of an optimal size and then ran Convolutional Neural Network (CNN) on each fragment to select phenotype-associated fragments. In the second step, using an overlapping window approach, we ran CNN on the selected fragments to calculate phenotype influence scores (PIS) and identify phenotype-associated SNPs based on PIS. In the third step, we ran CNN on all identified SNPs to develop a classification model. We tested our approach using genome-wide genotyping data for Alzheimer's disease (AD) (N=981; cognitively normal older adults (CN) =650 and AD=331). Our approach identified the well-known APOE region as the most significant genetic locus for AD. Our classification model achieved an area under the curve (AUC) of 0.82, which outperformed traditional machine learning approaches, Random Forest and XGBoost. By using a novel deep learning-based GWAS approach, we were able to identify AD-associated SNPs and develop a better classification model for AD.