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Biological and clinical insights from genetics of insomnia symptoms.

ABSTRACT: Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n?=?453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n?=?14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n?=?2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n?=?83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal glands. Evidence of shared genetic factors was found between frequent insomnia symptoms and restless legs syndrome, aging, and cardiometabolic, behavioral, psychiatric, and reproductive traits. Evidence was found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms, and subjective well-being.

SUBMITTER: Lane JM

PROVIDER: S-EPMC6415688 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Biological and clinical insights from genetics of insomnia symptoms.

Lane Jacqueline M JM Jones Samuel E SE Dashti Hassan S HS Wood Andrew R AR Aragam Krishna G KG van Hees Vincent T VT Strand Linn B LB Winsvold Bendik S BS Wang Heming H Bowden Jack J Song Yanwei Y Patel Krunal K Anderson Simon G SG Beaumont Robin N RN Bechtold David A DA Cade Brian E BE Haas Mary M Kathiresan Sekar S Little Max A MA Luik Annemarie I AI Loudon Andrew S AS Purcell Shaun S Richmond Rebecca C RC Scheer Frank A J L FAJL Schormair Barbara B Tyrrell Jessica J Winkelman John W JW Winkelmann Juliane J Hveem Kristian K Zhao Chen C Nielsen Jonas B JB Willer Cristen J CJ Redline Susan S Spiegelhalder Kai K Kyle Simon D SD Ray David W DW Zwart John-Anker JA Brumpton Ben B Frayling Timothy M TM Lawlor Deborah A DA Rutter Martin K MK Weedon Michael N MN Saxena Richa R

Nature genetics 20190225 3

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and ...[more]

PMID: 30804566

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Project description:Objective: Insomnia and depression are prevalent disorders that often co-occur. This study aimed to investigate the impact of clinically significant insomnia symptoms on the prevalence and clinical presentation of clinically significant depressive symptoms and vice versa. Methods: This study used data from the Korean Headache-Sleep Study (KHSS), a nationwide cross-sectional population-based survey regarding headache and sleep. Clinically significant insomnia symptoms were defined as Insomnia Severity Index (ISI) scores ≥ 10 and clinically significant depressive symptoms were defined as Patient Health Questionnaire-9 (PHQ-9) scores ≥ 10, respectively. We referred clinically significant insomnia symptoms and clinically significant depressive symptoms as insomnia symptoms and depressive symptoms, respectively. Results: Of 2,695 participants, 290 (10.8%) and 116 (4.3%) were classified as having insomnia and depressive symptoms, respectively. The prevalence of depressive symptoms was higher among participants with insomnia symptoms than in those without insomnia symptoms (25.9 vs. 1.7%, respectively, P < 0.001). Among participants with depressive symptoms, the PHQ-9 scores were not significantly different between participants with and without insomnia symptoms (P = 0.124). The prevalence of insomnia symptoms was significantly higher among participants with depressive symptoms than in those without depressive symptoms (64.7 vs. 8.3%, respectively, P < 0.001). The ISI scores were significantly higher among participants with insomnia and depressive symptoms than in participants with insomnia symptoms alone (P < 0.001). Conclusions: Participants with depressive symptoms had a higher risk of insomnia symptoms than did those without depressive symptoms. The severity of depressive symptoms did not significantly differ based on insomnia symptoms among participants with depressive symptoms; however, the severity of insomnia symptoms was significantly higher in participants with depressive symptoms than in those without depressive symptoms.

Project description:By running gene and pathway analyses for several smoking behaviours in the Tobacco and Genetics Consortium (TAG) sample of 74?053 individuals, 21 genes and several chains of biological pathways were implicated. Analyses were carried out using the HYbrid Set-based Test (HYST) as implemented in the Knowledge-based mining system for Genome-wide Genetic studies software. Fifteen genes are novel and were not detected with the single nucleotide polymorphism-based approach in the original TAG analysis. For quantity smoked, 14 genes passed the false discovery rate of 0.05 (corrected for multiple testing), with the top association signal located at the IREB2 gene (P=1.57E-37). Three genomic loci were significantly associated with ever smoked. The top signal is located at the noncoding antisense RNA transcript BDNF-AS (P=6.25E-07) on 11p14. The SLC25A21 gene (P=2.09E-08) yielded the top association signal in the analysis of smoking cessation. The 19q13 noncoding RNA locus exceeded the genome-wide significance in the analysis of age at initiation (P=1.33E-06). Pathways belonging to the Neuronal system pathways, harbouring the nicotinic acetylcholine receptor genes expressing the ? (CHRNA 1-9), ? (CHRNB 1-4), ?, ? and ? subunits, yielded the smallest P-values in the pathway analysis of the quantity smoked (lowest P=4.90E-42). Additionally, pathways belonging to 'a subway map of cancer pathways' regulating the cell cycle, mitotic DNA replication, axon growth and synaptic plasticity were found significantly enriched for genetic variants in ever smokers relative to never smokers (lowest P=1.61E-07). In addition, these pathways were also significantly associated with the quantity smoked (lowest P=4.28E-17). Our results shed light on one of the world's leading causes of preventable death and open a path to potential therapeutic targets. These results are informative in decoding the biological bases of other disease traits, such as depression and cancers, with which smoking shares genetic vulnerabilities.

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Biological and clinical insights from genetics of insomnia symptoms.

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Biological and clinical insights from genetics of insomnia symptoms.

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