Using SMR and HEIDI, we ultimately identified 5 genes causally associated with migraine with aura from the 8 targeted genes of contraindicated drugs that passed INTACT validation, among which three are common targets of Diuretics and Agents acting on the renin‐angiotensin system, and are associated with an increased risk of migraine with aura: ALMS1 (OR (95% CI) = 1.14 (1.051−1.237), PSMR = 1.61×10−3), GPATCH4 (OR (95% CI) = 1.783 (1.242−2.56), PSMR = 1.71×10−3), and ZKSCAN8P1 (OR (95% CI) = 1.409 (1.19−1.668), PSMR = 7.12×10−5). Here, REN is linked to migraine disorder.