Fully exploiting SNP arrays: a systematic review on the tools to extract underlying genomic structure

Abstract

Abstract Single nucleotide polymorphisms (SNPs) are the most abundant type of genomic variation and the most accessible to genotype in large cohorts. However, they individually explain a small proportion of phenotypic differences between individuals. Ancestry, collective SNP effects, structural variants, somatic mutations or even differences in historic recombination can potentially explain a high percentage of genomic divergence. These genetic differences can be infrequent or laborious to characterize; however, many of them leave distinctive marks on the SNPs across the genome allowing their study in large population samples. Consequently, several methods have been developed over the last decade to detect and analyze different genomic structures using SNP arrays, to complement genome-wide association studies and determine the contribution of these structures to explain the phenotypic differences between individuals. We present an up-to-date collection of available bioinformatics tools that can be used to extract relevant genomic information from SNP array data including population structure and ancestry; polygenic risk scores; identity-by-descent fragments; linkage disequilibrium; heritability and structural variants such as inversions, copy number variants, genetic mosaicisms and recombination histories. From a systematic review of recently published applications of the methods, we describe the main characteristics of R packages, command-line tools and desktop applications, both free and commercial, to help make the most of a large amount of publicly available SNP data.