As part of the PLoS Epigenetics Collection, Caroline Relton and George Davey Smith discuss the potential of epigenetics for the treatment and prevention of common complex diseases, including cancer

A Abbott

A Baccarelli

A Bird

A Izzotti

A Kong

AP Feinberg

AR Schuldiner

AS Dimas

B Delage

BT Heijmans

Caroline L. Relton

CC Wong

CM Shin

CN Tsai

CV Breton

D Haig

D Zhang

DT Hsiung

EH Wilker

EW Tobi

F Schembri

G Davey Smith

George Davey Smith

H Li

H Liu

HJ French

HK Seitz

HM Byun

HT Bjornsson

IC Weaver

J Campion

J Kaur

J Sauer

J Zacho

JK Kim

JM Launay

JM Philips

KC Kim

L Backdahl

L Chen

L Tarantini

LR Ferguson

M Hussain

M Kadota

M Pascual

M Teslovich

MC Myzak

MJ Drummond

MJ Meaney

MP Boks

N Timpson

NA Sheehan

NJ Timpson

O Aguilera

P Linsel-Nitschke

PW Laird

R Guerrero-Preston

R Lister

R Medzhitov

RA Waterland

RC Miranda

RD Nicholls

RF Thompson

RL Piekarz

RM Freathy

RP Talens

S Beck

S Boccia

S Radom Aizik

S Sharma

S Widiker

SF Gilbert

SJ Lewis

SL McGee

T Jenuwein

T Vaissiere

TO Tollefsbol

V Bollati

V Calvanese

V Emilsson

W Reik

WG Feero

Z Liu

English

PubMed

Caroline L Relton

Directory of Open Access Journals

PLoS Medicine

Epigenetic epidemiology of common complex disease: prospects for prediction, prevention, and treatment.

Relton Caroline L.

Davey Smith George

Public Library of Science (PLOS)

Epigenetic Epidemiology of Common Complex Disease: Prospects for Prediction, Prevention, and Treatment

Crossref

The epigenome records a variety of dietary, lifestyle, behavioral, and social cues, providing an interface between the environment and the genome. Epigenetic variation, whether genetically or environmentally determined, contributes to inter-individual variation in gene expression and thus to variation in common complex disease risk. Interventions based upon epigenetic agents, including DNA methyltransferase inhibitors and histone deacetylase inhibitors, have been in clinical use for many years, but their role outside treatment of specific cancers is not established. Epigenetic therapies will only be fruitful if epigenetic mechanisms are causally related to the disease being treated. Evidence linking epigenetic variation to specific disease phenotypes to date is lacking. Epidemiological approaches can be applied to help separate causal from non-causal associations. We propose the development of a Mendelian randomization approach (“genetical epigenomics”), which could help overcome the problems of confounding and reverse causation (when an association between epigenetic patterns and disease phenotype is observed but it is unknown whether the disease is causing changes to the epigenome or epigenetic changes are causal in disease pathogenesis).The epigenome records a variety of dietary, lifestyle, behavioral, and social cues, providing an interface between the environment and the genome. Epigenetic variation, whether genetically or environmentally determined, contributes to inter-individual variation in gene expression and thus to variation in common complex disease risk. Interventions based upon epigenetic agents, including DNA methyltransferase inhibitors and histone deacetylase inhibitors, have been in clinical use for many years, but their role outside treatment of specific cancers is not established. Epigenetic therapies will only be fruitful if epigenetic mechanisms are causally related to the disease being treated. Evidence linking epigenetic variation to specific disease phenotypes to date is lacking. Epidemiological approaches can be applied to help separate causal from non-causal associations. We propose the development of a Mendelian randomization approach (“genetical epigenomics”), which could help overcome the problems of confounding and reverse causation (when an association between epigenetic patterns and disease phenotype is observed but it is unknown whether the disease is causing changes to the epigenome or epigenetic changes are causal in disease pathogenesis)

Relton, Caroline L

Davey Smith, George

Explore Bristol Research

Epigenetic epidemiology of common complex disease:prospects for prediction, prevention, and treatment

A longitudinal study of epigenetic variation in twins.

Agening, chronic alcohol consumption and folate are determinnats of genomic DNAmethylation, p16 promoter methylation and the expression of p16 in the mouse colon.

Alcohol intake and blood pressure: a systematic review implementing Mendelian randomization approach.

Alcohol, ALDH2 and esophageal cancer: a meta-analysis which illustrates the potentials and limitations of a Mendelian randomization approach.

Aldehyde dehydrogenase 2 and head and neck cancer: a meta-analysis implementing a Mendelian randomization approach.

Allele-specific chromatin immunoprecipitation studies show genetic influence on chromatin state in human genome.

Assessing the effects of high methionine intake on DNA methylation.

Baccarelli A

Biological, clinical and population relevance of 95 loci for blood lipids.

Black carbon exposures, blood pressure and interactions with single nucleotide polymorphisms in microRNA processing genes.

C-reactive protein and its role in metabolic syndrome: Mendelian randomisation study.

Changes in DNA methylation patterns in subjects exposed to lowdose benzene.

Cigarette smoke induces demethylation of prometastatic oncogene synuclein-gamme in lung cancer cells by downregulation of DNMT3B.

Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology.

Common variation in the FTO gene alters diabetes-related metabolic traits to extent expected, given its effect on BMI.

Dietary manipulation of histone structure and function.

DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific.

DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging.

Does greater adiposity increase blood pressure and hypertension risk? Mendelian randomization using Fto/ Mc4r genotype.

Ecological developmental biology: Integrating epigenetics, medicine and evolution.

Effects of particulate matter on genomic DNA methylation content and iNOS promter methylation.

Epigenetic mechanisms in mammals.

Epigenetic modifiers: Basic understanding and clinical development.

Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue- and individual-specific DNA methylation patterns.

Epigenetic programming by maternal behaviour.

Epigenetic reprogramming in mammalian development.

Epigenetics and environment: a complex relationship.

Epigenetics and the biological definition of gene x environment interactions.

Epigenetics in cancer.

Essential amino acids increase miRNA-499, -208b and -23 in human skeletal muscle.

Evidence for microRNA involvement in exercise-associated neutrophil gene expression changes.

Exercise-induced histone modifications in human skeletal muscle.

Genetic control of individual differences in gene-specific methylation in human brain.

Genetic variation of regulatory systems.

Genetically elevated C-reactive protein and ischaemic vascular disease.

Genome-scale approaches to the epigenetics of common human disease.

Genomic medicine–An updated primer.

Global DNA methylation level in whole blood as a biomarker in head and neck squamous cell carcinoma.

Global hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds.

Heritable rather than agerelated and stochastic factors dominate variation in DNA methylation of the human IGF2/H19 locus.

High fat diet leads to a decreased methylation of the Mc4r gene in the obese BFMI and the lean B6 mouse lines.

Histone deacetylases as targets for dietary cancer preventive agents: lessons learned with butyrate, diallyl disulfide and sulforaphane.

How does body fat influence bone mass in childhood? A Mendelian randomisation approach.

Human DNA methylaomes at base pair resolution show widespread epigenomic differences.

Individuality and epigenetics in obesity.

Inferring gene transcriptional modulatory relations: a genetical genomics approach.

Inflammatory signalling as mediator of epigenetic modulation in tissue-specific chronic inflammation.

Inhalation of cigarette smoke induces regions of altered DNA methylation (RAMs) in SENCAR mouse lung.

Interindividual variation in epigenomic phenomena in humans.

Intraindividual change over time in DNA methylation with familial clustering.

Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease–a Mendelian randomization study.

Mendelian randomization and causal inference in observational epidemiology.

Mendelian randomization for strengthening causal inference in observational studies: applications to gene by environment interaction. Perspect Psychol Sci.

Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?

Methods of epigenetic analysis. In Tollefsbol TO. Epigenetics protocols.

MicroRNA: an emerging therapeutic target and intervention tool.

MicroRNAs as modulators of smoking-induced gene expression changes I human airway epithelium.

MicroRNAs: master regulators of ethanol abuse and toxicity?

Modulation of microRNA expression by budesonide, phenethyl isothiocyanate and cigarette smoke in mouse liver and lung.

Molecular mechanisms of alcohol-mediated carcinogenesis.

Parental origin of sequence variants associated with complex diseases.

Perceptions of epigenetics.

Persistent epigenetic differences associated with prenatal exposure to famine in humans.

Pollin TI (2010) Variation in blood lipids.

Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation.

Project set to map marks on genome.

Promoter hypermethylation in indian primary oral squamous cell carcinoma.

Rapid DNA methylation changes after exposure to traffic particles.

Repeated alcohol administration during adolescence causes changes in the mesolimbic dopaminergic and glutamatergic systems and promotes alcohol intake in the adult rat.

Smoking induces longlasting effects through a monoamine-oxidase epigenetic regulation.

The impact of genomic imprinting for neurobehavioural and developmental disorders.

The methylome: approaches for global DNA methylation profiling.

The power and the promise of DNA methylation markers.

The relationship of DNA methylation with age, gender and genotype in twins and healthy controls.

The role of epigenetics in ageing and age-related diseases. Ageing Res Rev 8: 268–276. Five Key Papers in the Field

The role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis. Cancer Sci. E-pub ahead of print. 18

Tissue specific dysregulation of DNA methylation in aging. Aging Cell,

Tobacco smoke induces polycomb-mediated repression of Dickkopf-1 in lung cancer cells.

Transcriptional control of the inflammatory response.

Translating the histone code.

Variation, patterns and temporal stability of DNA methylation: considerations for epigenetic epidemiology.

Weismann rules! OK? Epigenetics and the Lamarckian temptation.

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Epigenetic Epidemiology of Common Complex Disease: Prospects for Prediction, Prevention, and Treatment

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