Evidence map›Paper›PMID 38747164›Full record

ArticleHypertension (Dallas, Tex. : 1979)2024

Identification of the Molecular Components of Enhancer-Mediated Gene Expression Variation in Multiple Tissues Regulating Blood Pressure.

Or Yaacov, Prabhu Mathiyalagan, Hanna E Berk-Rauch, Santhi K Ganesh, Luke Zhu, Thomas J Hoffmann, Carlos Iribarren, Neil Risch, Dongwon Lee, Aravinda Chakravarti

Abstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Or YaacovCenter for Human Genetics and Genomics, NYU Grossman School of Medicine, New York, NY (O.Y., P.M., H.E.B.-R., L.Z., A.C.).ORCID 0000-0002-8496-2607
Prabhu MathiyalaganCenter for Human Genetics and Genomics, NYU Grossman School of Medicine, New York, NY (O.Y., P.M., H.E.B.-R., L.Z., A.C.).ORCID 0000-0002-8202-9266
Hanna E Berk-RauchCenter for Human Genetics and Genomics, NYU Grossman School of Medicine, New York, NY (O.Y., P.M., H.E.B.-R., L.Z., A.C.).ORCID 0000-0002-1238-1248
Santhi K GaneshDepartment of Internal Medicine & Department of Human Genetics, University of Michigan, Ann Arbor (S.K.G.).ORCID 0000-0002-3663-5249
Luke ZhuCenter for Human Genetics and Genomics, NYU Grossman School of Medicine, New York, NY (O.Y., P.M., H.E.B.-R., L.Z., A.C.).
Thomas J HoffmannDepartment of Epidemiology and Biostatistics (T.J.H., N.R.), University of California San Francisco.
Carlos IribarrenKaiser Permanente Northern California Division of Research, Oakland (C.I., N.R.).ORCID 0000-0001-5622-1839
Neil RischDepartment of Epidemiology and Biostatistics (T.J.H., N.R.), University of California San Francisco.ORCID 0000-0002-4126-2061
Dongwon LeeDepartment of Pediatrics, Division of Nephrology, Boston Children's Hospital, Boston & Harvard Medical School, MA (D.L.).ORCID 0000-0002-1568-2249
Aravinda ChakravartiCenter for Human Genetics and Genomics, NYU Grossman School of Medicine, New York, NY (O.Y., P.M., H.E.B.-R., L.Z., A.C.).ORCID 0000-0002-4264-2285

Funding

Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
Genomics of blood pressure-induced target organ damageR01HL128782 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CHAKRAVARTI, ARAVINDA · 2015 to 2018
$7.8M
Cardiac genetic effects across HLBS phenotypesR01HL141980 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CHAKRAVARTI, ARAVINDA · 2018 to 2019
$874k
NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL128782NHLBI NIH HHS R01 HL141980
6 · The paper itself

Abstract

backgroundInter-individual variation in blood pressure (BP) arises in part from sequence variants within enhancers modulating the expression of causal genes. We propose that these genes, active in tissues relevant to BP physiology, can be identified from tissue-level epigenomic data and genotypes of BP-phenotyped individuals.

methodsWe used chromatin accessibility data from the heart, adrenal, kidney, and artery to identify cis-regulatory elements (CREs) in these tissues and estimate the impact of common human single-nucleotide variants within these CREs on gene expression, using machine learning methods. To identify causal genes, we performed a gene-wise association test. We conducted analyses in 2 separate large-scale cohorts: 77 822 individuals from the Genetic Epidemiology Research on Adult Health and Aging and 315 270 individuals from the UK Biobank.

resultsWe identified 309, 259, 331, and 367 genes (false discovery rate <0.05) for diastolic BP and 191, 184, 204, and 204 genes for systolic BP in the artery, kidney, heart, and adrenal, respectively, in Genetic Epidemiology Research on Adult Health and Aging; 50% to 70% of these genes were replicated in the UK Biobank, significantly higher than the 12% to 15% expected by chance (

conclusionsOur work demonstrates the power of tissue-restricted comprehensive CRE analysis, followed by CRE-based expression prediction, for understanding BP regulation in relevant tissues and provides dual-modality supporting evidence, CRE and expression, for the causality genes.

Indexed as

Blood PressurePolymorphism, Single NucleotideAdrenal GlandsAdultAgedEnhancer Elements, GeneticFemaleGene Expression RegulationGenome-Wide Association StudyHumansHypertensionKidneyMaleMiddle Agedarteriesblood pressurechromatingene expressionkidney

Identifiers

PMID38747164
PMCPMC11168860

What OpenQuestion holds

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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.