Browsing by Subject "Neurodegenerative"

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    Transgenerational latent early-life associated regulation unites environment and genetics across generations
    (Future Science Group, 2016-03) Lahiri, Debomoy K.; Maloney, Bryan; Bayon, Baindu L.; Chopra, Nipun; White, Fletcher A.; Greig, Nigel H.; Nurnberger, John I.; Department of Psychiatry, IU School of Medicine
    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.