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Direct inference and control of genetic population structure from RNA sequencing data

Abstract:
RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s42003-023-05171-9

Authors

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Role:
Author
ORCID:
0000-0003-2199-5900
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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Tropical Medicine
Role:
Author
ORCID:
0000-0002-5179-650X
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Role:
Author
ORCID:
0000-0001-9620-8735

Contributors

Role:
Contributor


Publisher:
Springer Nature
Journal:
Communications Biology More from this journal
Volume:
6
Issue:
1
Article number:
804
Place of publication:
England
Publication date:
2023-08-02
Acceptance date:
2023-07-24
DOI:
EISSN:
2399-3642
Pmid:
37532769


Language:
English
Keywords:
Pubs id:
1500397
Local pid:
pubs:1500397
Deposit date:
2023-08-21
ARK identifier:

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