Identification of Novel Genetic Variants Associated with Insomnia and Migraine Comorbidity

Purpose: Although insomnia and migraine are often comorbid, the genetic association between insomnia and migraine remains unclear.This study aimed to identify susceptibility loci associated with insomnia and migraine comorbidity.Patients and Methods: We performed a genome-wide association study (GWAS) involving 1063 clinical outpatients at a tertiary hospital in Taiwan.Migraineurs with and without insomnia were genotyped using the Affymetrix Axiom Genome-Wide TWB 2.0.We performed association analyses for the entire cohort and stratified patients into the following subgroups: episodic migraine (EM), chronic migraine (CM), migraine with aura (MA), and migraine without aura (MoA).Potential correlations between SNPs and clinical indices in migraine patients with insomnia were examined using multivariate regression analysis. Results:The SNP rs1178326 in the gene HDAC9 was significantly associated with insomnia.In the EM, CM, MA, and MoA subgroups, we identified 30 additional susceptibility loci.Multivariate regression analysis showed that SNP rs1178326 also correlated with higher migraine frequency and the Migraine Disability Assessment (MIDAS) questionnaire score.Finally, two SNPs that had been previously reported in a major insomnia GWAS were also significant in our migraineurs, showing a concordant effect. Conclusion:In this GWAS, we identified several novel loci associated with insomnia in migraineurs in a Han Chinese population in Taiwan.These results provide insights into the possible genetic basis of insomnia and migraine comorbidity.