RT Journal Article
SR Electronic
T1 A reference haplotype panel for genome-wide imputation of short tandem repeats
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 277673
DO 10.1101/277673
A1 Shubham Saini
A1 Ileena Mitra
A1 Nima Mousavi
A1 Stephanie Feupe Fotsing
A1 Melissa Gymrek
YR 2018
UL http://biorxiv.org/content/early/2018/07/24/277673.abstract
AB Short tandem repeats (STRs) are involved in dozens of Mendelian disorders and have been implicated in a variety of complex traits. However, existing technologies focusing on single nucleotide polymorphisms (SNPs) have not allowed for systematic STR association studies. Here, we leverage next-generation sequencing data from 479 families to create a SNP+STR reference haplotype panel for genome-wide imputation of STRs into SNP data. Imputation achieved an average of 97% concordance between genotyped and imputed STR genotypes in an external dataset compared to 63% expected under a random model. Performance varied widely across STRs, with near perfect concordance at bi-allelic STRs vs. 70% at highly polymorphic forensics markers. We demonstrate that imputation increases power over individual SNPs to detect STR associations using simulated phenotypes and gene expression data. This resource will enable the first large-scale STR association studies using existing SNP datasets, and will likely yield new insights into complex traits.