Our Mendelian randomization analyses confirmed a lack of causal relationship between CRP and MDD but showed evidence consistent with a strong causal influence of higher BMI on increased CRP (β = 0.37, 95% CI = 0.36–0.39, p ≤ .001) and a bidirectional influence between reported trauma and MDD (OR trauma-MDD = 1.75, 95% CI = 1.49–2.07, p ≤ .001; OR MDD-trauma = 1.22, 95% CI = 1.18–1.27, p ≤ .001). The gene discussed is CRP; the disease is major depressive disorder.