Evidence map›Paper›PMID 27923400›Full record

ArticleGenome medicine2016

Allele-specific expression in the human heart and its application to postoperative atrial fibrillation and myocardial ischemia.

Martin I Sigurdsson, Louis Saddic, Mahyar Heydarpour, Tzuu-Wang Chang, Prem Shekar, Sary Aranki, Gregory S Couper, Stanton K Shernan, Jon G Seidman, Simon C Body and 1 more

2 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 25% of its field
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.

NCT00833313 unknown statusnot on this map

Gene Expression Profiling in Subjects With Postoperative Atrial Fibrillation After Cardiac Surgery (GENEXPRO Surg)

TypeobservationalSponsorBrigham and Women's HospitalRan2008 to 2025Enrolled350ConditionsAtrial FibrillationArmsAtrial biopsy
NCT00985049 recruitingnot on this map

Whole Genome Expression of Left Ventricular Myocardium During Cardiac Surgery

TypeobservationalSponsorBrigham and Women's HospitalRan2009 to 2025Enrolled350ConditionsCardiovascular Diseases
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 8 citations in OpenAlex.

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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

11 authors at 3 institutions in 1 country.

Martin I SigurdssonDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital / Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. martiningi@gmail.com.
Louis SaddicDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital / Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Mahyar HeydarpourDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital / Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Tzuu-Wang ChangDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital / Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Prem ShekarDivision of Cardiac Surgery, Department of Surgery, Brigham and Women's Hospital / Harvard Medical School, Boston, MA, USA.
Sary ArankiDivision of Cardiac Surgery, Department of Surgery, Brigham and Women's Hospital / Harvard Medical School, Boston, MA, USA.
Gregory S CouperDivision of Cardiac Surgery, Department of Surgery, Tufts Medical Center, Boston, MA, USA.
Stanton K ShernanDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital / Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Jon G SeidmanDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Simon C BodyDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital / Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Jochen D MuehlschlegelDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital / Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Harvard University · USBrigham and Women's Hospital · USTufts Medical Center · US

Funding

Defining Pathways from Gene Mutation to Heart FailureR01HL080494 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI CHEN, CHRISTOPHER S, SEIDMAN, CHRISTINE E · 2005 to 2024
$9.4M
Molecular Signaling in Hypertrophic CardiomyopathyR01HL084553 · NHLBI · HARVARD MEDICAL SCHOOL · PI SEIDMAN, JONATHAN G · 2007 to 2022
$5.9M
Genetics of gene expression in human left ventricular myocardiumR01HL118266 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MUEHLSCHLEGEL, JOCHEN DANIEL · 2013 to 2017
$2.3M
Identification of Genetic and Molecular Mechanisms of Atrial FibrillationR01HL098601 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI BODY, SIMON C · 2010 to 2014
$2.2M
NHLBI NIH HHS R01 HL080494NHLBI NIH HHS R01 HL084553NHLBI NIH HHS R01 HL098601NHLBI NIH HHS R01 HL118266
6 · The paper itself

Abstract

backgroundAllele-specific expression (ASE) is differential expression of each of the two chromosomal alleles of an autosomal gene. We assessed ASE patterns in the human left atrium (LA, n = 62) and paired samples from the left ventricle (LV, n = 76) before and after ischemia, and tested the utility of differential ASE to identify genes associated with postoperative atrial fibrillation (poAF) and myocardial ischemia.

methodsFollowing genotyping from whole blood and whole-genome sequencing of LA and LV samples, we called ASE using sequences overlapping heterozygous SNPs using rigorous quality control to minimize false ASE calling. ASE patterns were compared between cardiac chambers and with a validation cohort from cadaveric tissue. ASE patterns in the LA were compared between patients who had poAF and those who did not. Changes in ASE in the LV were compared between paired baseline and post-ischemia samples.

resultsASE was found for 3404 (5.1%) and 8642 (4.0%) of SNPs analyzed in the LA and LV, respectively. Out of 6157 SNPs with ASE analyzed in both chambers, 2078 had evidence of ASE in both LA and LV (p < 0.0001). The SNP with the greatest ASE difference in the LA of patients with and without postoperative atrial fibrillation was within the gelsolin (GSN) gene, previously associated with atrial fibrillation in mice. The genes with differential ASE in poAF were enriched for myocardial structure genes, indicating the importance of atrial remodeling in the pathophysiology of AF. The greatest change in ASE between paired post-ischemic and baseline samples of the LV was in the zinc finger and homeodomain protein 2 (ZHX2) gene, a modulator of plasma lipids. Genes with differential ASE in ischemia were enriched in the ubiquitin ligase complex pathway associated with the ischemia-reperfusion response.

conclusionsOur results establish a pattern of ASE in the human heart, with a high degree of shared ASE between cardiac chambers as well as chamber-specific ASE. Furthermore, ASE analysis can be used to identify novel genes associated with (poAF) and myocardial ischemia.

Indexed as

AllelesGene Expression RegulationGenotypeAgedAnimalsAtrial FibrillationCardiac Surgical ProceduresFemaleGenotyping TechniquesHeart VentriclesHigh-Throughput Nucleotide SequencingHumansMaleMiceMiddle AgedMyocardial Ischemia

Identifiers

PMID27923400
PMCPMC5139013
OpenAlexW2560165361

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.