GWAIS-Web: A Fast and Secure Web Service for Epistasis Detection in Genome-wide Association Interaction Studies

Abstract

AbstractMotivationGenome-wide association interaction studies (GWAIS) are becoming increasingly important as estimates of genetic interactions at the genome-wide level using genome-wide data from hundreds of thousands of individuals from large biobanks showed that non-additive genetic variance plays a role in complex human traits in addition to additive genetic effects identified in genome-wide association studies (GWAS). However, a comprehensive genome-wide search for all combinations of second-order (SNPxSNP) or third-order (SNPxSNPxSNP) associations using millions of SNP markers is a very computationally intensive task, especially when hundreds of thousands or, in the near future, even millions of individuals can be studied with GWAS datasets. The runtime so far exceeds years, even if the search is performed on a multicore CPU server system.ResultsWe developedGWAIS-Web, a web service for fast analysis of genome-wide interactions with case-control GWAS datasets. By using a hybrid combination of graphics-processing units (GPUs) and field-programmable gate arrays (FPGAs),GWAIS-Webspeeds up epistasis detection methods for binary traits by a factor of more than 2000, allowing an exhaustive SNP-SNP GWAIS with a GWAS data set of one million SNPs and 500,000 individuals to complete within one day, which would take more than five years on a regular CPU server system. The user can choose between different methods for epistasis detection, such as logistic regression, BOOST, mutual information (MI) and others, with calculations in double precision and including on-the-fly filtering of correlated results based on linkage disequilibrium (LD). Due to the underlying common data structure ofGWAIS-Web, all methods can be combined and processed together on-the-fly without increasing the runtime. The user can choose between 2nd order (pairwise) and 3rd order tests and can also limit the search to selected chromosomal regions.GWAIS-Weboffers a high level of security through optional 2-factor authentication, encrypted connections and the protection of GWAS/user account data in accordance with the European General Data Protection Regulation (GDPR).AvailabilityGWAIS-Webis freely available athttps://hybridcomputing.ikmb.uni-kiel.de. The stand-alone softwareHybridGWAIScan be downloaded athttps://github.com/ikmb/hybridgwais.Supplementary informationSupplementary data are available online.