ABSTRACT
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.
