title: Transgenerational latent early-life associated regulation unites environment and genetics across generations.
abstract: 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.
authors.affiliation: Department of Psychiatry, Stark Neurosciences Research Institute, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, IN 46202, USA.|Department of Medical & Molecular Genetics, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, IN 46202, USA.
authors.forename: Debomoy K
authors.initials: DK
authors.lastname: Lahiri
authors.affiliation: Department of Psychiatry, Stark Neurosciences Research Institute, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, IN 46202, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Maloney
authors.affiliation: Department of Medical & Molecular Genetics, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, IN 46202, USA.
authors.forename: Baindu L
authors.initials: BL
authors.lastname: Bayon
authors.affiliation: Department of Psychiatry, Stark Neurosciences Research Institute, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, IN 46202, USA.
authors.forename: Nipun
authors.initials: N
authors.lastname: Chopra
authors.affiliation: Department of Anesthesia, Stark Neurosciences Research Institute, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, IN 46202, USA.
authors.forename: Fletcher A
authors.initials: FA
authors.lastname: White
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
authors.affiliation: Department of Psychiatry, Stark Neurosciences Research Institute, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, IN 46202, USA.|Department of Medical & Molecular Genetics, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, IN 46202, USA.
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D000818:Animals; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D006801:Humans; D008297:Male; D018811:Maternal Exposure; D008954:Models, Biological; D010300:Parkinson Disease / Q000235:genetics; D011247:Pregnancy; D012559:Schizophrenia / Q000235:genetics
keywords: aging; childhood; development; epigenetics; experiences; insult; intergenerational; late life; neurodegenerative; nutrition; post traumatic