April 24, 2021Disease Models & MechanismsOpen Access

Integrative genomic analysis of blood pressure and related phenotypes in rats

Q: What is the clinical evidence from this study?

Study design: Other. Population: Hypertension (animal model) (n=8704). Intervention: Genomic analysis and pharmacological intervention vs. Wistar Kyoto rats (WKY). Primary outcome: Identification of causal genes and pathways for blood pressure traits.

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Key result

Integrative genomic analysis identified 26 potential target genes, including rat homologs of human TWAS loci, that regulate blood pressure and related phenotypes in a rat polygenic hypertension model.

Why the study?

A substantial gap remains between statistical evidence from human genome-wide association studies and functional comprehension of the underlying mechanisms governing these associations.

Population

Spontaneously hypertensive rats, stroke-prone SHR, and Wistar Kyoto rats

Comparison

Hypertensive rat strains vs non-hypertensive Wistar Kyoto rats

Design

Integrative genomic analysis in rat models

Authors

FTFumihiko TakeuchiNational Institutes of Health YLYi-Qiang LiangShenyang Aerospace University MIMasato IsonoNational Center for Global Health and Medicine

Discussion

Member takes

Implication

No immediate clinical implications; leaves open whether rat homologs translate to human hypertension targets.

Structured PICO

Population

Integrative genomic analysis of blood pressure and related phenotypes in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP), and Wistar Kyoto rats (WKY).

Exposure

Integrative genomic analysis including whole-genome sequencing, transcriptome profiling, genome-wide linkage scans, fine congenic mapping, pharmacological intervention, and comparative analysis with transcriptome-wide association study (TWAS) datasets.

Comparator

Non-hypertensive control strain, Wistar Kyoto rats (WKY).

Outcome

Identification of causal genes and causal pathways for blood pressure and related phenotypes.surrogate

Integrative genomic analysis in hypertensive rat models identified key genes and pathways, particularly the kallikrein-kinin/renin-angiotensin systems, underlying polygenic hypertension.

Limitations

Higher statistical power is required to detect QTLs with a complex genetic architecture and less prominent effect.
Multiple layers of evidence are indispensable to draw conclusions about causality, as inter-strain differential gene expression can be either the cause or consequence of BP elevation.
Inter-species comparative analysis using TWAS datasets does not achieve sufficient coverage of BP loci.
Biological impacts of some causal genes or pathways may not be comparable between species.
The possible presence of sex-specific QTLs needs to be further explored for BP and related phenotypes in rats.

Cite This Study

Takeuchi et al. (2021) studied Hypertension (animal model) (n=8,704). Genomic analysis and pharmacological intervention vs. Wistar Kyoto rats (WKY) was evaluated on Identification of causal genes and pathways for blood pressure traits. Integrative genomic analysis identified 26 potential target genes, including rat homologs of human TWAS loci, that regulate blood pressure and related phenotypes in a rat polygenic hypertension model.

synapsesocial.com/papers/6a6590d66bff4e8afbc08061 https://doi.org/10.1242/dmm.048090

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Integrative genomic analysis of blood pressure and related phenotypes in rats

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Integrative genomic analysis of blood pressure and related phenotypes in rats

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Also Consider

Also Consider