Family-based association study of chromosome 6p12.2-p21.1 migraine locus

Background.— One of the genome‐wide linkage studies performed in migraine has yielded a significant linkage of migraine (with and without aura) with markers located at 6p12.2‐21.1. This locus (named MIGR3) has not been replicated in the only genome‐wide association scan study performed to date or in previous genome‐wide linkage studies. Objective.— Our objective had been to replicate the MIGR3 locus performing a family‐based association study. Methods.— A sample of 594 subjects belonging to 134 migraine families of diverse complexity underwent genotyping for the markers previously published as linked at 6p12.2‐21.1 migraine locus. Family‐based association test, under different models of inheritance, and also the model‐free TDT analysis were performed. Results.— The best result was obtained with the D6S1650 marker under the additive model (rank [S observed] = 265.0; permuted P = .0006), using family‐based association test program (HBAT subprogram). Similar results were obtained with the model‐free TDTPHASE algorithm (P < .0001, corrected). Nominal significant P values were obtained for D6S1630, D6S452, and D6S257. After correction for multiple testing with the stratified false‐discovery rate, all markers showed significant association (P < .0001). Conclusion.— We corroborated that the MIGR3 locus at 6p12 is a genetic risk for migraine with and without aura. (Headache 2012;52:393‐399)