N Gladish1,2, S M Merrill1, Michael S Kobor3. 1. Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, BC Children's Hospital Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. 2. School of Medicine, Department of Epidemiology & Public Health, Stanford University, 1701 Page Mill Road, Palo Alto, CA, 94304-1210, USA. 3. Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, BC Children's Hospital Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. msk@bcchr.ca.
Abstract
PURPOSE OF REVIEW: There is a great deal of interest regarding the biological embedding of childhood trauma and social exposures through epigenetic mechanisms, including DNA methylation (DNAm), but a comprehensive understanding has been hindered by issues of limited reproducibility between studies. This review presents a summary of the literature on childhood trauma and DNAm, highlights issues in the field, and proposes some potential solutions. RECENT FINDINGS: Investigations of the associations between DNAm and childhood trauma are commonly performed using candidate gene approaches, specifically involving genes related to neurological and stress pathways. Childhood trauma is defined in a wide range of ways in several societal contexts. However, although variations in DNAm are frequently found in stress-related genes, unsupervised epigenome-wide association studies (EWAS) have shown limited reproducibility both between studies and in relating these changes to exposures. The reproducibility of childhood trauma DNAm studies, and the field of social epigenetics in general, may be improved by increasing sample sizes, standardizing variables, making use of effect size thresholds, collecting longitudinal and intervention samples, appropriately accounting for known confounding factors, and applying causal analysis wherever possible, such as "two-step epigenetic Mendelian randomization."
PURPOSE OF REVIEW: There is a great deal of interest regarding the biological embedding of childhood trauma and social exposures through epigenetic mechanisms, including DNA methylation (DNAm), but a comprehensive understanding has been hindered by issues of limited reproducibility between studies. This review presents a summary of the literature on childhood trauma and DNAm, highlights issues in the field, and proposes some potential solutions. RECENT FINDINGS: Investigations of the associations between DNAm and childhood trauma are commonly performed using candidate gene approaches, specifically involving genes related to neurological and stress pathways. Childhood trauma is defined in a wide range of ways in several societal contexts. However, although variations in DNAm are frequently found in stress-related genes, unsupervised epigenome-wide association studies (EWAS) have shown limited reproducibility both between studies and in relating these changes to exposures. The reproducibility of childhood trauma DNAm studies, and the field of social epigenetics in general, may be improved by increasing sample sizes, standardizing variables, making use of effect size thresholds, collecting longitudinal and intervention samples, appropriately accounting for known confounding factors, and applying causal analysis wherever possible, such as "two-step epigenetic Mendelian randomization."
Authors: Karin B Michels; Alexandra M Binder; Sarah Dedeurwaerder; Charles B Epstein; John M Greally; Ivo Gut; E Andres Houseman; Benedetta Izzi; Karl T Kelsey; Alexander Meissner; Aleksandar Milosavljevic; Kimberly D Siegmund; Christoph Bock; Rafael A Irizarry Journal: Nat Methods Date: 2013-10 Impact factor: 28.547
Authors: Sumaiya A Islam; Sarah J Goodman; Julia L MacIsaac; Jelena Obradović; Ronald G Barr; W Thomas Boyce; Michael S Kobor Journal: Epigenetics Chromatin Date: 2019-01-02 Impact factor: 4.954