Journal Article

pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms

Wahl, Simone, Grallert, Harald, Waldenberger, Melanie, Peters, Annette, Müller-Nurasyid, Martina, Meitinger, Thomas, Theis, Fabian J., Adamski, Jerzy, Molnos, Sophie, Baumbach, Clemens, Strauch, Konstantin, Wang-Sattler, Rui, Suhre, Karsten, Gieger, Christian, Kastenmüller, Gabi

2017

Overview

Background Genome-wide association studies allow us to understand the genetics of complex diseases. Human metabolism provides information about the disease-causing mechanisms, so it is usual to investigate the associations between genetic variants and metabolite levels. However, only considering genetic variants and their effects on one trait ignores the possible interplay between different “omics” layers. Existing tools only consider single-nucleotide polymorphism (SNP)–SNP interactions, and no practical tool is available for large-scale investigations of the interactions between pairs of arbitrary quantitative variables. Results We developed an R package called pulver to compute p-values for the interaction term in a very large number of linear regression models. Comparisons based on simulated data showed that pulver is much faster than the existing tools. This is achieved by using the correlation coefficient to test the null-hypothesis, which avoids the costly computation of inversions. Additional tricks are a rearrangement of the order, when iterating through the different “omics” layers, and implementing this algorithm in the fast programming language C++. Furthermore, we applied our algorithm to data from the German KORA study to investigate a real-world problem involving the interplay among DNA methylation, genetic variants, and metabolite levels. Conclusions The pulver package is a convenient and rapid tool for screening huge numbers of linear regression models for significant interaction terms in arbitrary pairs of quantitative variables. pulver is written in R and C++, and can be downloaded freely from CRAN at https://cran.r-project.org/web/packages/pulver/ .

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Algorithm / Algorithms / Analysis / Bioinformatics / Biomedical and Life Sciences / C plus plus / C++ (programming language) / Computation / Computational Biology/Bioinformatics / Computer Appl. in Life Sciences / Computer Simulation / Correlation coefficient / Correlation coefficients / CpG Islands - genetics / Deoxyribonucleic acid / DNA / DNA methylation / Epigenetics / Genetic variance / Genetics / Genome-wide association studies / Genomes / Health aspects / Humans / Hypotheses / Inversions / Life Sciences / Linear Models / Linear regression interaction term / Mathematical models / Metabolism / Metabolites / Microarrays / Physiological aspects / Polymorphism / Polymorphism, Single Nucleotide - genetics / Programming languages / Regression analysis / Regression models / Results and data / Single-nucleotide polymorphism / SNP–CpG interaction / Software / Studies / Time Factors / Values / Variables