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Nat Commun. 2018 Oct 23;9(1):4397. doi: 10.1038/s41467-018-06694-0.

A reference haplotype panel for genome-wide imputation of short tandem repeats.

Author information

1
Department of Computer Science and Engineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
2
Bioinformatics and Systems Biology Program, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
3
Department of Electrical and Computer Engineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
4
Department of Biomedical Informatics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
5
Department of Computer Science and Engineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. mgymrek@ucsd.edu.
6
Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. mgymrek@ucsd.edu.

Abstract

Short tandem repeats (STRs) are involved in dozens of Mendelian disorders and have been implicated in complex traits. However, genotyping arrays used in genome-wide association studies focus on single nucleotide polymorphisms (SNPs) and do not readily allow identification of STR associations. We leverage next-generation sequencing (NGS) from 479 families to create a SNP + STR reference haplotype panel. Our panel enables imputing STR genotypes into SNP array data when NGS is not available for directly genotyping STRs. Imputed genotypes achieve mean concordance of 97% with observed genotypes in an external dataset compared to 71% expected under a naive model. Performance varies widely across STRs, with near perfect concordance at bi-allelic STRs vs. 70% at highly polymorphic repeats. Imputation increases power over individual SNPs to detect STR associations with gene expression. Imputing STRs into existing SNP datasets will enable the first large-scale STR association studies across a range of complex traits.

PMID:
30353011
PMCID:
PMC6199332
DOI:
10.1038/s41467-018-06694-0
[Indexed for MEDLINE]
Free PMC Article

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