Department of Psychology and Neuroscience, University of Colorado Boulder, Muenzinger, 345 UCB, 1905 Colorado Avenue, Boulder, Colorado 80309-0345, USA
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The nascent field of epigenetics has attracted growing attention in research on pre-natal alcohol exposure, alcohol use and alcohol use disorders. Animal models and studies in community and clinical human samples have provided tantalising clues that epigenetic patterns may be associated with alcohol use and alcohol-related outcomes. However, the reversible and plastic nature of epigenetic patterns means that questions about causality and direction of effect remain unresolved. This review highlights two particularly refractory challenges to establishing causality in epigenetic studies that use living human subjects: confounding variables and reverse causation. Experimental studies (e.g., using alcohol self-administration tasks) and quasi-experimental designs (e.g., longitudinal studies, sibling comparison designs and instrumental variable approaches) may be used to control for potential confounds and explore the causal impact of epigenetic processes (e.g., DNA methylation) on alcohol-related outcomes.
No single design is a ‘magic bullet’, but the careful use of a combination of designs will help to strengthen causal inferences in epigenetic research in clinical and community samples.