INS and Headache: Although a relatively small SNP-based heritability z-score was obtained for fasting proinsulin (z < 7), which may lead to an inaccurate heritability estimate, our LCV analyses found significant evidence for partial genetic causality between fasting proinsulin and both migraine (GCP = 0.74, SE = 0.18, P = 9.67 × 10–9) and headache (GCP = 0.85, SE = 0.11, P = 8.05 × 10–22) (Supplementary Table S20).