Transgenerational latent early-life associated regulation unites environment and genetics across generations

Debomoy K. Lahiri, Bryan Maloney, Baindu L. Bayon, Nipun Chopra, Fletcher A. White, Nigel H. Greig, John I. Nurnberger

Research output: Contribution to journalArticle

9 Scopus citations


The origin of idiopathic diseases is still poorly understood. The latent early-life associated regulation (LEARn) model unites environmental exposures and gene expression while providing a mechanistic underpinning for later-occurring disorders. We propose that this process can occur across generations via transgenerational LEARn (tLEARn). In tLEARn, each person is a 'unit' accumulating preclinical or subclinical 'hits' as in the original LEARn model. These changes can then be epigenomically passed along to offspring. Transgenerational accumulation of 'hits' determines a sporadic disease state. Few significant transgenerational hits would accompany conception or gestation of most people, but these may suffice to 'prime' someone to respond to later-life hits. Hits need not produce symptoms or microphenotypes to have a transgenerational effect. Testing tLEARn requires longitudinal approaches. A recently proposed longitudinal epigenome/envirome-wide association study would unite genetic sequence, epigenomic markers, environmental exposures, patient personal history taken at multiple time points and family history.

Original languageEnglish (US)
Pages (from-to)373-387
Number of pages15
Issue number3
StatePublished - Mar 2016


  • aging
  • childhood
  • development
  • epigenetics
  • experiences
  • insult
  • intergenerational
  • late life
  • neurodegenerative
  • nutrition
  • post traumatic

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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