Evidence map›Paper›PMID 34883445›Full record

ArticleEBioMedicine2021

Lifestyle and Genetic Factors Modify Parent-of-Origin Effects on the Human Methylome.

Yanni Zeng, Carmen Amador, Chenhao Gao, Rosie M Walker, Stewart W Morris, Archie Campbell, Azra Frkatović, Rebecca A Madden, Mark J Adams, Shuai He and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Review
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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

18 authors at 6 institutions in 4 countries.

Yanni ZengFaculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address: zengyn5@mail.sysu.edu.cn.
Carmen AmadorMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Chenhao GaoFaculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
Rosie M WalkerCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK; Centre for Clinical Brain Sciences, Chancellor's Building, The University of Edinburgh, Edinburgh, UK.
Stewart W MorrisCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Archie CampbellCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Azra FrkatovićGenos Glycoscience Research Laboratory, Borongajska cesta 83h, 10000 Zagreb, Croatia.
Rebecca A MaddenDivision of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
Mark J AdamsDivision of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
Shuai HeSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, 510060, China.
Andrew D BretherickMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Caroline HaywardMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
David J PorteousCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
James F WilsonMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
Kathryn L EvansCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Andrew M McIntoshDivision of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
Pau NavarroMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. Electronic address: pau.navarro@ed.ac.uk.
Chris S HaleyMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK; Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK. Electronic address: chris.haley@ed.ac.uk.
Edinburgh Cancer Research · GBInstitute of Genetics and Cancer · GBSun Yat-sen University · CNUniversity of Edinburgh · GBGenos (Croatia) · HRRoslin Institute · GB

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Translational Research Support CoreP30ES000002 · NIEHS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI SUSAN A KORRICK · 1985 to 2026
$44.6M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Task Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2M
CARDIOVASCULAR HEALTH STUDY (CHS) - TASK AREA C, STUDY CLOSEOUT75N92021D00006 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE · 2021 to 2024
$8.4M
A Longitudinal Epigenetic Study of AtherosclerosisR01HL135009 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI LIU, YONGMEI · 2017 to 2020
$5.8M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1M
TO EXERCISE OPTION PERIOD ONE (1) FOR TASK AREA A - MESA CORE OPERATIONS, FIELD CENTER.75N92020D00004 · NHLBI · NORTHWESTERN UNIVERSITY · PI SIEGEL, JONATHAN H · 2020 to 2025
$4.5M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00006 · NHLBI · UNIVERSITY OF MINNESOTA · PI PANKOW, JAMES S · 2020 to 2025
$4.4M
Biotechnology and Biological Sciences Research Council BB/I014144/1CLC NIH HHS 75N90020D00002CLC NIH HHS 75N90020D00003Medical Research Council MC_PC_U127592696Medical Research Council MC_UU_00007/10NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS 75N92021D00006NHLBI NIH HHS 75N92022D00007NHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL101250NHLBI NIH HHS R01 HL126477NHLBI NIH HHS R01 HL135009NIAID NIH HHS 75N93020D00002NIA NIH HHS RF1 AG054474NIDA NIH HHS 75N95020D00002NIDA NIH HHS 75N95020D00003NIDA NIH HHS 75N95020D00004NIDA NIH HHS 75N95020D00005NIDA NIH HHS 75N95020D00007NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK101921NIEHS NIH HHS 75N96020D00002NIEHS NIH HHS 75N96020D00003NIH HHS 75N98020D00007ORFDO NIH HHS 75N99020D00002ORFDO NIH HHS 75N99020D00003ORFDO NIH HHS 75N99020D00004ORFDO NIH HHS 75N99020D00005ORFDO NIH HHS 75N99020D00006ORFDO NIH HHS 75N99020D00007Wellcome Trust
6 · The paper itself

Abstract

backgroundparent-of-origin effects (POE) play important roles in complex disease and thus understanding their regulation and associated molecular and phenotypic variation are warranted. Previous studies mainly focused on the detection of genomic regions or phenotypes regulated by POE. Understanding whether POE may be modified by environmental or genetic exposures is important for understanding of the source of POE-associated variation, but only a few case studies addressing modifiable POE exist.

methodsin order to understand this high order of POE regulation, we screened 101 genetic and environmental factors such as 'predicted mRNA expression levels' of DNA methylation/imprinting machinery genes and environmental exposures. POE-mQTL-modifier interaction models were proposed to test the potential of these factors to modify POE at DNA methylation using data from Generation Scotland: The Scottish Family Health Study(N=2315).

findingsa set of vulnerable/modifiable POE-CpGs were identified (modifiable-POE-regulated CpGs, N=3). Four factors, 'lifetime smoking status' and 'predicted mRNA expression levels' of TET2, SIRT1 and KDM1A, were found to significantly modify the POE on the three CpGs in both discovery and replication datasets. We further identified plasma protein and health-related phenotypes associated with the methylation level of one of the identified CpGs.

interpretationthe modifiable POE identified here revealed an important yet indirect path through which genetic background and environmental exposures introduce their effect on DNA methylation, motivating future comprehensive evaluation of the role of these modifiers in complex diseases.

fundingNSFC (81971270),H2020-MSCA-ITN(721815), Wellcome (204979/Z/16/Z,104036/Z/14/Z), MRC (MC_UU_00007/10, MC_PC_U127592696), CSO (CZD/16/6,CZB/4/276, CZB/4/710), SFC (HR03006), EUROSPAN (LSHG-CT-2006-018947), BBSRC (BBS/E/D/30002276), SYSU, Arthritis Research UK, NHLBI, NIH.

Indexed as

DNA MethylationCpG IslandsDioxygenasesDNA-Binding ProteinsEpigenomicsGene Expression RegulationGenomic ImprintingHistone DemethylasesHumansLife StylePhenotypeQuantitative Trait LociSirtuin 1DioxygenasesDNA-Binding ProteinsHistone DemethylasesKDM1A protein, humanSIRT1 protein, humanSirtuin 1TET2 protein, humanDNA methylationDNA methylation machinery genesinteraction (modification) effectmQTLparent-of-origin effectsmoking

Identifiers

PMID34883445
PMCPMC8654798
OpenAlexW4226336542

What OpenQuestion holds

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LicenceCC BY
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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.