Evidence map›Paper›PMID 40493452›Full record

ArticleCell reports2025

Physiological role and mechanisms of action for a long noncoding haplotype region.

Hong Xue, Manoj K Mishra, Yong Liu, Pengyuan Liu, Michael Grzybowski, Rajan Pandey, Kristie Usa, Mark A Vanden Avond, Niharika Bala, Abdel A Alli and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Hong XueDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Manoj K MishraDepartment of Physiology, University of Arizona College of Medicine - Tucson, Tucson, AZ, USA.
Yong LiuDepartment of Physiology, University of Arizona College of Medicine - Tucson, Tucson, AZ, USA.
Pengyuan LiuDepartment of Physiology, University of Arizona College of Medicine - Tucson, Tucson, AZ, USA.
Michael GrzybowskiDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Rajan PandeyDepartment of Physiology, University of Arizona College of Medicine - Tucson, Tucson, AZ, USA.
Kristie UsaDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Mark A Vanden AvondDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Niharika BalaDepartment of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida College of Medicine, Gainesville, FL, USA.
Abdel A AlliDepartment of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida College of Medicine, Gainesville, FL, USA.
Allen W CowleyDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Qiongzi QiuDepartment of Physiology, University of Arizona College of Medicine - Tucson, Tucson, AZ, USA.
Andrew S GreeneThe Jackson Laboratory, Bar Harbor, ME, USA.
Sridhar RaoVersiti Blood Research Institute, Milwaukee, WI, USA; Department of Pediatrics, Division of Hematology, Oncology, and Transplantation, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
Caitlin C O'MearaDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Aron M GeurtsDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: ageurts@mcw.edu.
Mingyu LiangDepartment of Physiology, University of Arizona College of Medicine - Tucson, Tucson, AZ, USA. Electronic address: mliang1@arizona.edu.

Funding

Sequencing Coordination and Data Analysis CoreP01HL149620 · NHLBI · UNIVERSITY OF ARIZONA · PI LIANG, MINGYU · 2020 to 2024
$11.8M
RIGERR: Resources for Investigating Genetic and Epigenetic Regulation of Renal DiseaseRC2DK129964 · NIDDK · UNIVERSITY OF ARIZONA · PI MINGYU LIANG · 2022 to 2026
$4.9M
NHLBI NIH HHS P01 HL149620NIDDK NIH HHS RC2 DK129964
6 · The paper itself

Abstract

Direct targeting of noncoding genomic regions harboring common sequence variants associated with human traits through in vivo animal model studies and precise genome editing in human cells is essential for closing the critical gap between genetic discoveries and physiological understanding. However, such investigation has been impractical for many of these variants as they are in haplotypes containing multiple single-nucleotide polymorphisms (SNPs) spanning thousands of base pairs and have small effect sizes. We developed an integrated approach to address this challenge, combining an efficient two-step technique to precisely edit large haplotypes in human induced pluripotent stem cells and orthologous region deletion in phenotypically permissive animal models. As proof of principle, we applied this approach to examine a blood pressure-associated locus with a noncoding haplotype containing 11 SNPs spanning 17.4 kbp. We found a robust blood pressure effect of nearly 10 mmHg and identified the physiological and molecular mechanisms involved.

Indexed as

HaplotypesAnimalsBlood PressureCRISPR-Cas SystemsGene EditingHumansInduced Pluripotent Stem CellsMicePolymorphism, Single Nucleotideanimal modelblood pressurechromatin interactionCP: Genomicsgenome editinghaplotypehypertensioninduced pluripotent stem cellsnoncodingsaltsingle-nucleotide polymorphism

Identifiers

PMID40493452
PMCPMC12263090

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.