Evidence map›Paper›PMID 28985495›Full record

ArticleAmerican journal of human genetics2017

Mendelian Randomization Analysis Identifies CpG Sites as Putative Mediators for Genetic Influences on Cardiovascular Disease Risk.

Tom G Richardson, Jie Zheng, George Davey Smith, Nicholas J Timpson, Tom R Gaunt, Caroline L Relton, Gibran Hemani

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

Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 3 pooled it
10.1field-weighted citation impact, top 2% 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

43 citing papers in PubMed, 3 syntheses or guidelines pooled it, 77 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

7 authors at 1 institution in 1 country.

Tom G RichardsonMRC Integrative Epidemiology Unit, Bristol Medical School (Population Health Sciences), University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. Electronic address: tom.g.richardson@bristol.ac.uk.
Jie ZhengMRC Integrative Epidemiology Unit, Bristol Medical School (Population Health Sciences), University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
George Davey SmithMRC Integrative Epidemiology Unit, Bristol Medical School (Population Health Sciences), University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Nicholas J TimpsonMRC Integrative Epidemiology Unit, Bristol Medical School (Population Health Sciences), University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Tom R GauntMRC Integrative Epidemiology Unit, Bristol Medical School (Population Health Sciences), University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Caroline L ReltonMRC Integrative Epidemiology Unit, Bristol Medical School (Population Health Sciences), University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Gibran HemaniMRC Integrative Epidemiology Unit, Bristol Medical School (Population Health Sciences), University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
University of Bristol · GB

Funding

Medical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_PC_15049Medical Research Council MC_PC_16067Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/2Medical Research Council MC_UU_12013/3Medical Research Council MC_UU_12013/8Wellcome Trust 202802/Z/16/Z
6 · The paper itself

Abstract

The extent to which genetic influences on cardiovascular disease risk are mediated by changes in DNA methylation levels has not been systematically explored. We developed an analytical framework that integrates genetic fine mapping and Mendelian randomization with epigenome-wide association studies to evaluate the causal relationships between methylation levels and 14 cardiovascular disease traits. We identified ten genetic loci known to influence proximal DNA methylation which were also associated with cardiovascular traits after multiple-testing correction. Bivariate fine mapping provided evidence that the individual variants responsible for the observed effects on cardiovascular traits at the ADCY3 and ADIPOQ loci were potentially mediated through changes in DNA methylation, although we highlight that we are unable to reliably separate causality from horizontal pleiotropy. Estimates of causal effects were replicated with results from large-scale consortia. Genetic variants and CpG sites identified in this study were enriched for histone mark peaks in relevant tissue types and gene promoter regions. Integrating our results with expression quantitative trait loci data, we provide evidence that variation at these regulatory regions is likely to also influence gene expression levels at these loci.

Indexed as

CpG IslandsDNA MethylationPolymorphism, Single NucleotideQuantitative Trait LociAdenylyl CyclasesAdiponectinCardiovascular DiseasesChildCohort StudiesFemaleGene Expression RegulationGenome, HumanGenome-Wide Association StudyHumansMendelian Randomization AnalysisPhenotypeadenylate cyclase 3Adenylyl CyclasesAdiponectinADIPOQ protein, humancardiovascular diseasecausal inferenceDNA methylationepigenome-wide association studiesMendelian randomization

Identifiers

PMID28985495
PMCPMC5630190
OpenAlexW2761786170

What OpenQuestion holds

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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.