Evidence map›Paper›PMID 27036880›Full record

ArticleGenome biology2016

Systematic identification of genetic influences on methylation across the human life course.

Tom R Gaunt, Hashem A Shihab, Gibran Hemani, Josine L Min, Geoff Woodward, Oliver Lyttleton, Jie Zheng, Aparna Duggirala, Wendy L McArdle, Karen Ho and 4 more

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

Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 374 papers, 18 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
374citing papers in PubMed, 18 pooled it
38.6field-weighted citation impact, top 1% 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

374 citing papers in PubMed, 18 syntheses or guidelines pooled it, 644 citations in OpenAlex.

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  19. Genome-wide association study of aromatase inhibitor discontinuation due to musculoskeletal symptoms.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022
    Trial
  20. Article

314 more citing papers are in PubMed but not listed here.

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

14 authors at 2 institutions in 2 countries.

Tom R GauntMRC Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK. tom.gaunt@bristol.ac.uk.ORCID http://orcid.org/0000-0003-0924-3247
Hashem A ShihabMRC Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Gibran HemaniMRC Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Josine L MinMRC Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Geoff WoodwardMRC Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Oliver LyttletonAvon Longitudinal Study of Parents and Children (ALSPAC) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Jie ZhengMRC Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Aparna DuggiralaAvon Longitudinal Study of Parents and Children (ALSPAC) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Wendy L McArdleAvon Longitudinal Study of Parents and Children (ALSPAC) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Karen HoAvon Longitudinal Study of Parents and Children (ALSPAC) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Susan M RingMRC Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
David M EvansMRC Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
George Davey SmithMRC Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
Caroline L ReltonMRC Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
University of Bristol · GBTranslational Research Institute · AU

Funding

Biotechnology and Biological Sciences Research Council BB/I025263/1Biotechnology and Biological Sciences Research Council BB/I025751/1Medical Research Council G1000427Medical Research Council G1001799Medical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/2Medical Research Council MC_UU_12013/4Medical Research Council MC_UU_12013/8Medical Research Council MR/N01104X/1Wellcome Trust 102215Wellcome Trust 102215/2/13/2
6 · The paper itself

Abstract

backgroundThe influence of genetic variation on complex diseases is potentially mediated through a range of highly dynamic epigenetic processes exhibiting temporal variation during development and later life. Here we present a catalogue of the genetic influences on DNA methylation (methylation quantitative trait loci (mQTL)) at five different life stages in human blood: children at birth, childhood, adolescence and their mothers during pregnancy and middle age.

resultsWe show that genetic effects on methylation are highly stable across the life course and that developmental change in the genetic contribution to variation in methylation occurs primarily through increases in environmental or stochastic effects. Though we map a large proportion of the cis-acting genetic variation, a much larger component of genetic effects influencing methylation are acting in trans. However, only 7 % of discovered mQTL are trans-effects, suggesting that the trans component is highly polygenic. Finally, we estimate the contribution of mQTL to variation in complex traits and infer that methylation may have a causal role consistent with an infinitesimal model in which many methylation sites each have a small influence, amounting to a large overall contribution.

conclusionsDNA methylation contains a significant heritable component that remains consistent across the lifespan. Our results suggest that the genetic component of methylation may have a causal role in complex traits. The database of mQTL presented here provide a rich resource for those interested in investigating the role of methylation in disease.

Indexed as

DNA MethylationGenetic VariationQuantitative Trait LociAdolescentChildChild, PreschoolCpG IslandsDatabases, GeneticDNAEpigenesis, GeneticFemaleGenetic Association StudiesHumansInfant, NewbornMiddle AgedPregnancyDNACohortDNA methylationGenetic associationMethylation quantitative trait locimQTL

Identifiers

PMID27036880
PMCPMC4818469
OpenAlexW2316537321

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.