Mendelian Randomization Identifies Lipidomic Signatures of Depression Risk That Are Partly Reflected in Cortisol-Induced Membrane Remodeling and Modulated by St. John's Wort Extract (Ze 117).

Across the 49 discovery lipid hits, 20 were also mapped by the Ottensmann panel; of those, 18 (90%) showed a concordant direction of effect in the Finnish sample, and eight (40%) were nominally significant ( p < 0.05) for an MDD association ( Figure S4 ).

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While the overlap between Ze 117-regulated lipids and GSMR hits did not reach statistical significance in permutation testing ( p > 0.05), the trend was noteworthy—especially considering that many lipids showed changes in the expected direction (i.e., Ze 117 increasing levels of lipids that are protective in MDD).

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