Cross-trait gene-based overlap analysis identified 33 genes significantly associated (Pgene-based < 3.85 × 10−6) with migraine and T2D, and 11 genes associated with headache and T2D, with 7 genes (EHMT2, SLC44A4, PLEKHA1, CFDP1, TMEM170A, CHST6, and BCAR1) common between them. This evidence concerns the gene PLEKHA1 and type 2 diabetes mellitus.