Lahiri, Debomoy K.Maloney, BryanBayon, Baindu L.Chopra, NipunWhite, Fletcher A.Greig, Nigel H.Nurnberger, John I.2017-08-022017-08-022016-03Lahiri, D. K., Maloney, B., Bayon, B. L., Chopra, N., White, F. A., Greig, N. H., & Nurnberger, J. I. (2016). Transgenerational latent early-life associated regulation unites environment and genetics across generations. Epigenomics, 8(3), 373–387. http://doi.org/10.2217/epi.15.117https://hdl.handle.net/1805/13717The 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.en-USPublisher PolicyAgingChildhoodDevelopmentEpigeneticsExperiencesInsultIntergenerationalLate lifeNeurodegenerativeNutritionPost traumaticArticle