Evidence map›Paper›PMID 36737504›Full record

ArticleHepatology international2023

Differential DNA methylation of steatosis and non-alcoholic fatty liver disease in adolescence.

Phillip E Melton, M A Burton, K A Lillycrop, K M Godfrey, S Rauschert, D Anderson, G C Burdge, T A Mori, L J Beilin, O T Ayonrinde and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hepatology international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. 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

18 authors.

Phillip E MeltonMenzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Private Bag 23, Hobart, TAS, 7000, Australia. phillip.melton@utas.edu.au.ORCID http://orcid.org/0000-0003-4026-2964
M A BurtonSchool of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
K A LillycropBiological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK.
K M GodfreyNIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
S RauschertTelethon Kids Institute, The University of Western Australia, Perth, Australia.
D AndersonTelethon Kids Institute, The University of Western Australia, Perth, Australia.
G C BurdgeSchool of Human Health and Development, Faculty of Medicine, University of Southampton, Southampton, UK.
T A MoriMedical School, The University of Western Australia, Perth, Australia.
L J BeilinMedical School, The University of Western Australia, Perth, Australia.
O T AyonrindeMedical School, The University of Western Australia, Perth, Australia.
J M CraigMCRI, Royal Children's Hospital, Flemington Road, Parkville, VIC, Australia.
J K OlynykDepartment of Gastroenterology and Hepatology, Fiona Stanley and Fremantle Hospitals, Murdoch, WA, Australia.
J D HolbrookMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
C E PennellUniversity of Newcastle, Newcastle, NSW, Australia.
W H OddyMenzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Private Bag 23, Hobart, TAS, 7000, Australia.
E K MosesMenzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Private Bag 23, Hobart, TAS, 7000, Australia.
L A AdamsMedical School, The University of Western Australia, Perth, Australia.
R C HuangTelethon Kids Institute, The University of Western Australia, Perth, Australia.

Funding

Medical Research Council MC_UU_12011/4National Health and Medical Research Council 1053384National Health and Medical Research Council 1059711National Health and Medical Research Council 1136046National Health and Medical Research Council 1142858National Health and Medical Research Council 353514National Health and Medical Research Council 403981NIHR BioResource NF-SI-0515-10042
6 · The paper itself

Abstract

BACKGROUND AND

aimsEpigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks. APPROACH AND

resultsWe performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10

conclusionsWe identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.

Indexed as

DNA MethylationNon-alcoholic Fatty Liver DiseaseAdolescentAdultBiomarkersDNAEpigenesis, GeneticHumansBiomarkersDNAANK1EpigeneticsEWASMIR10APTPRN2

Identifiers

PMID36737504
PMCPMC9897882

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.