HiGwas: How to compute longitudinal GWAS data in population designs

Abstract

Summary: Genome-wide association studies (GWAS), particularly designed with thousands and thousands of single-nucleotide polymorphisms (SNPs) (big p) genotyped on tens of thousands of subjects (small n), are encountered by a major challenge of p ≪ n. Although the integration of longitudinal information can significantly enhance a GWAS's power to comprehend the genetic architecture of complex traits and diseases, an additional challenge is generated by an autocorrelative process. We have developed several statistical models for addressing these two challenges by implementing dimension reduction methods and longitudinal data analysis. To make these models computationally accessible to applied geneticists, we wrote an R package of computer software, HiGwas, designed to analyze longitudinal GWAS datasets. Functions in the package encompass single SNP analyses, significance-level adjustment, preconditioning and model selection for a high-dimensional set of SNPs. HiGwas provides the estimates of genetic parameters and the confidence intervals of these estimates. We demonstrate the features of HiGwas through real data analysis and vignette document in the package.