A broad overview of genotype imputation:Standard guidelines,approaches,and future investigations in genomic association studies

The advent of genomic big data and the statistical need for reaching significant results have led genome-wide association studies to be ravenous of a huge number of genetic markers scattered along the whole genome.Since its very beginning,the so-called genotype imputation served this purpose;this statistical and inferential procedure based on a known reference panel opened the theoretical possibility to extend association analyses to a greater number of polymorphic sites which have not been previously assayed by the used technology.In this review,we present a broad overview of the genotype imputation process,showing the most known methods and presenting the main areas of interest,with a closer look to the most up-to-date approaches and a deeper understanding of its usage in the presentday genomic landscape,shedding a light on its future developments and investigation areas.