Genetic risk factors of chronic insomnia disorder
Background: Chronic insomnia disorder (CID) affects 3.5 million Canadians. Despite its high prevalence, we do not fully understand the underlying mechanisms of CID. Genetic studies of insomnia contribute to better understanding its biological basis. The latest two genome-wide association studies (GWAS) suggest that MEIS1 gene, previously associated with restless legs syndrome (RLS), is independently associated to insomnia. However, the GWAS phenotyping method was limited and the finding was not yet replicated. Objective: Evaluate the association between MEIS1 and CID. If MEIS1 is pleiotropic to CID and RLS, the minor allele frequency of MEIS1 variants will be equivalent in CID patients with and without RLS. Methods: Overall, 646 CID patients participated in the study. We genotyped three MEIS1 variants. To confirm our results, we compared the allelic and genotypic distributions of the CID cohort to ethnically matched controls and RLS cases from the French Canadian cohort. Results: Patients were diagnosed by sleep specialists and 26% of the sample were diagnosed with CID+RLS. We find significant differences in allele and genotype distributions between CID-only and CID+RLS groups. Allele and genotype distributions of the three MEIS1 SNPs were similar in between CID-only and control groups and in between CID+RLS and RLS-only groups (all p>0.05). Conclusion: Our data confirms the association between MEIS1 and RLS but it does not support the pleiotropic effect of MEIS1 in CID. Further, our study highlights the critical importance of phenotyping and the need to carefully isolate CID from other disorders that can cause sleep difficulties, particularly RLS.
GWAS MEIS1 Sleep disorders Sleep genetics Insomnia genetics Chronic insomnia disorder Restless legs syndrome Genome wide association study Phenotyping