Analysis of Extremely Obese Individuals Using Deep Learning Stacked Autoencoders and Genome-Wide Genetic Data

TL;DR

This study employs deep learning autoencoders to analyze genome-wide genetic data, uncovering complex SNP interactions that improve classification of extremely obese individuals beyond traditional GWAS methods.

Contribution

It introduces a novel deep learning approach using stacked autoencoders to identify epistatic SNP interactions for obesity classification, addressing limitations of linear GWAS.

Findings

Achieved high classification accuracy with AUC of 0.975 using 2000 compressed units.

Demonstrated the effectiveness of non-linear deep learning models in capturing SNP interactions.

Improved obesity prediction performance compared to traditional GWAS-based methods.

Abstract

The aetiology of polygenic obesity is multifactorial, which indicates that life-style and environmental factors may influence multiples genes to aggravate this disorder. Several low-risk single nucleotide polymorphisms (SNPs) have been associated with BMI. However, identified loci only explain a small proportion of the variation ob-served for this phenotype. The linear nature of genome wide association studies (GWAS) used to identify associations between genetic variants and the phenotype have had limited success in explaining the heritability variation of BMI and shown low predictive capacity in classification studies. GWAS ignores the epistatic interactions that less significant variants have on the phenotypic outcome. In this paper we utilise a novel deep learning-based methodology to reduce the high dimensional space in GWAS and find epistatic interactions between SNPs for classification purposes. SNPs were filtered based on the effects associations have with BMI. Since Bonferroni adjustment for multiple testing is highly conservative, an important proportion of SNPs involved in SNP-SNP interactions are ignored. Therefore, only SNPs with p-values < 1x10-2 were considered for subsequent epistasis analysis using stacked auto encoders (SAE). This allows the nonlinearity present in SNP-SNP interactions to be discovered through progressively smaller hidden layer units and to initialise a multi-layer feedforward artificial neural network (ANN) classifier. The classifier is fine-tuned to classify extremely obese and non-obese individuals. The best results were obtained with 2000 compressed units (SE=0.949153, SP=0.933014, Gini=0.949936, Lo-gloss=0.1956, AUC=0.97497 and MSE=0.054057). Using 50 compressed units it was possible to achieve (SE=0.785311, SP=0.799043, Gini=0.703566, Logloss=0.476864, AUC=0.85178 and MSE=0.156315).