title: Biological embedding of early-life exposures and disease risk in humans: a role for DNA methylation.
abstract: BACKGROUND
  Following wider acceptance of 'the thrifty phenotype' hypothesis and the convincing evidence that early-life exposures can influence adult health even decades after the exposure, much interest has been placed on the mechanisms through which early-life exposures become biologically embedded.
  
  
  METHODS
  In this review, we summarize the current literature regarding biological embedding of early-life experiences. To this end, we conducted a literature search to identify studies investigating early-life exposures in relation to DNA methylation changes. In addition, we summarize the challenges faced in investigations of epigenetic effects, stemming from the peculiarities of this emergent and complex field. A proper systematic review and meta-analyses were not feasible given the nature of the evidence.
  
  
  RESULTS
  We identified seven studies on early-life socio-economic circumstances, 10 studies on childhood obesity and six studies on early-life nutrition all relating to DNA methylation changes that met the stipulated inclusion criteria. The pool of evidence gathered, albeit small, favours a role of epigenetics and DNA methylation in biological embedding, but replication of findings, multiple comparison corrections, publication bias and causality are concerns remaining to be addressed in future investigations.
  
  
  CONCLUSIONS
  Based on these results, we hypothesize that epigenetics, in particular DNA methylation, is a plausible mechanism through which early-life exposures are biologically embedded. This review describes the current status of the field and acts as a stepping stone for future, better designed investigations on how early-life exposures might become biologically embedded through epigenetic effects.
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Department of Electron Microscopy / Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors: Christiana A
authors: CA
authors: Demetriou
authors: Karin
authors: K
authors: van Veldhoven
authors: Caroline
authors: C
authors: Relton
authors: Silvia
authors: S
authors: Stringhini
authors: Kyriacos
authors: K
authors: Kyriacou
authors: Paolo
authors: P
authors: Vineis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002648:Child; D002664:Child Nutritional Physiological Phenomena / Q000502:physiology*; D002675:Child, Preschool; D019175:DNA Methylation / Q000502:physiology*; D004198:Disease Susceptibility / Q000209:etiology*; D004781:Environmental Exposure / Q000009:adverse effects; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D006801:Humans; D007223:Infant; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D063766:Pediatric Obesity / Q000150:complications; D012307:Risk Factors; D012959:Socioeconomic Factors; D055815:Young Adult
keywords: Biological embedding; DNA methylation, epigenetics; body mass index; early-life nutrition; early-life socio-economic status