Abstract
Insomnia is one of the most prevalent and burdensome mental disorders worldwide, affecting between 10–20% of adults and up to 48% of the geriatric population. It is further associated with substance usage and dependence, as well other psychiatric disorders. In this study, we combined electronic health record (EHR) derived phenotypes and genotype information to conduct a genome wide analysis of insomnia in a 18,055 patient cohort. Diagnostic codes were used to identify 3,135 patients with insomnia. Our genome-wide association study (GWAS) identified one novel genomic risk locus on chromosome 8 (lead SNP rs17052966, p = 4.53 × 10−9, odds ratio = 1.28, se = 0.04). The heritability analysis indicated that common SNPs accounts for 7% (se = 0.02, p = 0.015) of phenotypic variation. We further conducted a large-scale meta-analysis of our results and summary statistics of two recent insomnia GWAS and 13 significant loci were identified. The genetic correlation analysis yielded a strong positive genetic correlation between insomnia and alcohol use (rG = 0.56, se = 0.14, p < 0.001), nicotine use (rG = 0.50, se = 0.12, p < 0.001) and opioid use (rG = 0.43, se = 0.18, p = 0.02) disorders, suggesting a significant common genetic risk factors between insomnia and substance use.
Highlights
Insomnia is a highly prevalent sleep disorder characterized by the inability to fall asleep or maintain sleep[1] and affects 10–20% of the adult population[2,3]
Genetic contributions to insomnia have been demonstrated in both family and twin studies with the reported heritability being estimated at 25–45%8
We evaluated the genetic correlations between insomnia and a series of clinical conditions extracted from Partners Biobank using codified data
Summary
Insomnia is a highly prevalent sleep disorder characterized by the inability to fall asleep or maintain sleep[1] and affects 10–20% of the adult population[2,3] It is characterized by heterogeneous phenotypes and equifinality, which might reflect different underlying causal mechanisms[4], including life style, stress and molecular mechanisms (for a review, see[5]). Another study using survey data of soldiers in the Army Study To Assess Risk and Resilience in Servicemembers (STARRS) study identified one significant locus[15] These studies identified genetic correlations between insomnia and various clinical conditions, such as schizophrenia, type 2 diabetes, and depression[13,15]. Electronic health records (EHRs) from large medical institutes comprise a uniquely valuable data source to help identify genetic associations within very specific clinical conditions[21]
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