The epidemiologic study of DNA methylation (DNAm) and mental health is a burgeoning area, but confounding and reverse causation remain important to know about. Whether use of non-brain tissues is appropriate when investigating brain phenotypes depends on the hypothesis and whether the goal is causality or to identify biomarkers. Look-ups of the correspondence between DNAm in blood and brain and use of Mendelian randomization (MR) can be done to follow-up, to some degree, on the causal nature of some findings. Social scientists, health methodologists (epidemiologists), and basic scientists-thinkers who view epigenetics and mental health from different perspectives-can come together in the design and framing of findings to avoid pitfalls and innovate beyond what each could do alone.
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