The relation of a blood DNA methylation score with six-year depression course and risk factors

In EPICv2-profiled blood from 731 individuals in NESDA, a blood DNAm depression score (MD-MS) is elevated in lifetime MDD versus controls (β=0.137, p=0.012).

• Why it matters: Major depressive disorder risk is shaped by psychosocial, environmental, biological, and lifestyle factors, but it is unclear how a blood DNAm depression signature tracks lifetime exposure and MDD course.
• What they did: MD-MS was computed from the top 15 EWAS-significant depression sites in EPICv2 blood at baseline (N=366) and six-year follow-up (N=365), then tested with linear mixed effects for 8 clinical and 16 MDD risk factors and MDD trajectories.
• The result: Lower social activity, CRP, triglycerides, and fasting glucose were positively associated with MD-MS, while higher neighborhood air pollution was negatively associated; chronic MDD showed consistently higher MD-MS (β=0.295, p=0.001).

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