51 polymorphisms showed a replicated (p<0.05 in both subsamples and total sample) effect in interaction with lifetime depression for migraine, from which 26 could be associated with ADGRL2 (also known as LPHN2) on chromosome 1, with rs7412827 being a downstream gene variant, while the others were intron variants. This evidence concerns the gene ADGRL2 and major depressive disorder.