Evidence map›Paper›PMID 28957329›Full record

ArticlePloS one2017

Uncovering the DNA methylation landscape in key regulatory regions within the FADS cluster.

Elaheh Rahbar, Hannah C Ainsworth, Timothy D Howard, Gregory A Hawkins, Ingo Ruczinski, Rasika Mathias, Michael C Seeds, Susan Sergeant, James E Hixson, David M Herrington and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 15% 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.

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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  10. Observational
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Allele-specific methylation in theClinical epigenetics · 2018
    Article
  18. Article
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

12 authors at 3 institutions in 1 country.

Elaheh RahbarDepartment of Biomedical Engineering, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.ORCID http://orcid.org/0000-0001-5941-7917
Hannah C AinsworthDepartment of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
Timothy D HowardCenter for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
Gregory A HawkinsCenter for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
Ingo RuczinskiDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
Rasika MathiasDivision of Allergy and Clinical Immunology Department of Medicine, The Johns Hopkins University, Baltimore, MD, United States of America.
Michael C SeedsDepartment of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
Susan SergeantDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
James E HixsonDepartment of Epidemiology, Human Genetics and Environmental Sciences, Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, United States of America.
David M HerringtonDepartment of Internal Medicine, Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
Carl D LangefeldDepartment of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
Floyd H ChiltonDepartment of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
Wake Forest University · USJohns Hopkins University · USThe University of Texas Health Science Center at Houston · US

Funding

Genomic and Proteomic Architecture of AtherosclerosisR01HL111362 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI HERRINGTON, DAVID MCLEOD · 2012 to 2021
$17.2M
The Wake Forest Center for Botanical Lipids and Inflammatory Disease PreventionP50AT002782 · NCCIH · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI CHILTON, FLOYD H · 2005 to 2014
$15.3M
SNPs and Extent of Atherosclerosis (SEA) StudyU01HL080443 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI HERRINGTON, DAVID MCLEOD · 2006 to 2009
$8.7M
Role of PUFA-Gene Interactions in Health DisparitiesR01AT008621 · NCCIH · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI FLOYD H CHILTON, Susan Schembre · 2016 to 2026
$5.4M
An Integrated Investigation of the Interaction Between PUFAs and Genetic Variants in Trauma and Critical CareK25HL133611 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI RAHBAR, ELAHEH · 2017 to 2021
$841k
NCCIH NIH HHS P50 AT002782NCCIH NIH HHS R01 AT008621NHLBI NIH HHS K25 HL133611NHLBI NIH HHS R01 HL111362NHLBI NIH HHS U01 HL080443
6 · The paper itself

Abstract

Genetic variants near and within the fatty acid desaturase (FADS) cluster are associated with polyunsaturated fatty acid (PUFA) biosynthesis, levels of several disease biomarkers and risk of human disease. However, determining the functional mechanisms by which these genetic variants impact PUFA levels remains a challenge. Utilizing an Illumina 450K array, we previously reported strong allele-specific methylation (ASM) associations (p = 2.69×10-29) between a single nucleotide polymorphism (SNP) rs174537 and DNA methylation of CpG sites located in the putative enhancer region between FADS1 and FADS2, in human liver tissue. However, this array only featured 20 CpG sites within this 12kb region. To better understand the methylation landscape within this region, we conducted bisulfite sequencing of the region between FADS1 and FADS2. Liver tissues from 50 male subjects (27 European Americans, 23 African Americans) were obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, and used to ascertain the genotype at rs174537 and methylation status across the region of interest. Associations between rs174537 genotype and methylation status of 136 CpG sites were determined. Age-adjusted linear regressions were used to assess ASM associations with rs174537 genotype. The majority of CpG sites (117 out of 136, 86%) exhibited high levels of methylation with the greatest variability observed at three key regulatory regions-the promoter regions for FADS1 and FADS2 and a putative enhancer site between the two genes. Eight CpG sites within the putative enhancer region displayed significant (FDR p <0.05) ASM associations with rs174537. These data support the concept that both genetic and epigenetic factors regulate PUFA biosynthesis, and raise fundamental questions as to how genetic variants such as rs174537 impact DNA methylation in distant regulatory regions, and ultimately the capacity of tissues to synthesize PUFAs.

Indexed as

Multigene FamilyAdultBlack or African AmericanCpG IslandsDelta-5 Fatty Acid DesaturaseDemographyDNA MethylationFatty Acid DesaturasesGenotypeHumansPolymorphism, Single NucleotideRegulatory Sequences, Nucleic AcidSequence Analysis, DNAWhite PeopleDelta-5 Fatty Acid DesaturaseFADS1 protein, humanFADS2 protein, humanFatty Acid Desaturases

Identifiers

PMID28957329
PMCPMC5619705
OpenAlexW2758416553

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.