Identification of Novel Genetic Variants Associated with Insomnia and Migraine Comorbidity

Abstract

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.

Potential genetic and epigenetic mechanisms in insomnia: A systematic review

“…In this framework, GWAS SNPs genetic pre‐disposition to insomnia were found to have a significant causal effect on the risk of some mental conditions such as major depression, bipolar disorder type II, schizophrenia, autism spectrum disorder, alcohol, nicotine and opioid use, attention‐deficit/hyperactivity disorder, anxiety and post‐traumatic stress disorder (PTSD), and suicidal behaviours with reverse causality observed for major depression, nicotine use, and PTSD only (Jansen, Dolinoy, et al, 2019, Jansen, Watanabe, et al, 2019; Gao et al, 2019; Song et al, 2020; Pasman et al, 2020; Lewis et al, 2020; Cai et al, 2021; Huang et al, 2021; Carpena et al, 2021; Watanabe et al, 2022; Sun et al, 2022; Baranova et al, 2022; Zhou et al, 2022; Nassan et al, 2022). Similarly, GWAS SNPs genetic pre‐disposition to insomnia were found to have a significant causal one‐way effect on the risk of some medical conditions including: coronavirus disease 2019 (COVID‐19) susceptibility (Peng et al, 2022), cognitive impairment, neurodegenerative conditions (Sun et al, 2020; Zhang et al, 2022), cardiovascular diseases (Jansen, Dolinoy, et al, 2019; Jansen, Watanabe, et al, 2019; Jia et al, 2022; Liu et al, 2021; Zheng et al, 2020), diabetes, cardio‐metabolic risks (Gao et al, 2020; Jansen, Dolinoy, et al, 2019; Jansen, Watanabe, et al, 2019; Liu et al, 2021; Liu et al, 2022), increasing the odds of reporting pain conditions (An et al, 2022; Broberg et al, 2021; Chu et al, 2021; Shu et al, 2022) and for other medical conditions (Bao et al, 2022; He et al, 2022; Huo et al, 2021; Zha et al, 2021).…”