Prospects for Epigenetic Epidemiology

Foley, Debra L.; Craig, Jeffrey M.; Morley, Ruth; Olsson, Craig A.; Dwyer, Terence; Smith, Katherine R.; Saffery, Richard

doi:10.1093/aje/kwn380

Cited by 220 publications

(167 citation statements)

References 171 publications

(165 reference statements)

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“…9 Evidence supporting a change in DNA methylation with time has led some to suggest that smoking, diet, and other epidemiologic risk factors may influence these epigenetic changes. [47][48][49][50] Gender. Many studies have found that global DNA methylation was higher in males than in females.…”

Section: Wbc Methylation and Diseasementioning

confidence: 99%

DNA methylation in white blood cells

et al. 2011

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Section: Wbc Methylation and Diseasementioning

confidence: 99%

DNA methylation in white blood cells

et al. 2011

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“…This is exemplified by the epigenetic mark of DNA methylation, which influences a gene's transcriptional potential and plays a role in differentiation (Reik 2007;Brunner et al 2009;Huang and Fan 2010) and aging Teschendorff et al 2010). Disruption of epigenetic profile is a ubiquitous feature of cancers and is likely to play a role in the etiology of other complex diseases (van Vliet et al 2007;Foley et al 2009). …”

mentioning

confidence: 99%

Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence

Gordon¹,

Joo²,

Powell³

et al. 2012

Genome Res.

258

216

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Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of~20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.

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“…Ao mesmo tempo em que outros mecanismos genéticos e moleculares começam a ser explorados, os estudos epidemiológicos mantêm a busca pelos fatores ambientais que influenciam o surgimento das patologias mentais, mas adotando a mesma suposição da etiologia complexa que surge da interação gene-ambiente (JABLONKA, 2004;WONG;PETRONIS, 2005;OS;RUTTEN;POULTON, 2008;OH;PETRONIS, 2008;FOLEY et al, 2009;RUTTEN;MILL, 2009;DICK;RILEY;KENDLER, 2010). Também no caso da pesquisa epidemiológica, a hipótese epigenética parece solucionar antigos problemas e questões não resolvidas e pode, inclusive, redirecionar os objetivos e as características das investigações na área.…”

Section: As Pesquisas Epidemiológicas E a Influência Do Ambienteunclassified

A epigenética como nova hipótese etiológica no campo psiquiátrico contemporâneo

Freitas-Silva

Ortega

2014

Physis

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Resumo: Nas últimas décadas, as teorias neurocientíficas passaram a ser adotadas como explicação primordial para a etiologia dos transtornos mentais. Com o objetivo de encontrar os fundamentos dos transtornos, as investigações priorizaram a carga genética e o funcionamento cerebral. A partir da valorização da determinação biológica das doenças e do surgimento de variadas tecnologias de pesquisa médica, aventou-se a possibilidade de que as causas dos transtornos fossem, finalmente, compreendidas. No entanto, diversas dificuldades e desafios marcam o projeto neurocientífico de fundamentação biológica da etiologia das doenças. A introdução recente da noção de epigenética no campo psiquiátrico vem sendo considerada fundamental para renovar a esperança de compreensão da etiologia dos transtornos. A partir da análise de artigos de revisão, o presente trabalho tem como objetivos examinar a apropriação da noção de epigenética pelo campo psiquiátrico contemporâneo, identificando suas origens e descrevendo suas principais características, e refletir sobre as consequências de sua adoção. Além de contribuir para a redefinição das teses etiológicas no campo psiquiátrico, a noção de epigenética impõe uma reconfiguração do conhecimento genético e, em certa medida, do próprio projeto determinista e reducionista de fundamentação biológica dos transtornos mentais, permitindo interpretações mais nuançadas sobre as neurociências e a psiquiatria contemporânea. Palavras-chave: Psiquiatria biológica; neurociências; etiologia.

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Prospects for Epigenetic Epidemiology

Cited by 220 publications

References 171 publications

DNA methylation in white blood cells

DNA methylation in white blood cells

Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence

A epigenética como nova hipótese etiológica no campo psiquiátrico contemporâneo

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