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• W2788173172 abstract "Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes, but underlying pathophysiological processes and causal relationships with disease are poorly understood. We performed a genome-wide association study using 453,379 participants of European ancestry with self-reported insomnia symptoms in the UK Biobank using BOLT-LMM. We measured heritability and performed association tests adjusting for age, sex, genetic ancestry and genotyping array (~14 million variants). We performed follow-up analysis stratified by sex. We performed tissue-based and pathway enrichment analyses using FUMA, Magma, and Pascal. Pair-wise genetic correlation analyses to 224 traits were performed using LDSC. Two-sample Mendelian randomization (MR) was performed in MR-base. We identified 57 genome-wide significant loci for self-reported insomnia symptoms (n=453,379) and confirmed their impact on self-reported insomnia symptoms in the HUNT study (n=14,923 cases, 47,610 controls), physician diagnosed insomnia in the Partners Biobank (n=2,217 cases, 14,420 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n=83,726). Our results show enrichment of genes involved in ubiquitin-mediated proteolysis, phototransduction and muscle development and enrichment of genes expressed in specific brain regions, skeletal muscle and adrenal gland. Evidence of shared genetic factors is found between frequent insomnia symptoms and restless legs syndrome, cardio-metabolic traits, neuroticism, smoking behavior, depressive symptoms/disorder, cognitive measures, subjective well-being, proxy longevity measures and reproductive traits. Evidence is found for a possible causal link between insomnia symptoms and coronary heart disease, depressive symptoms and subjective well-being (p<0.001). This study highlights the genetic architecture of frequent or persistent insomnia symptoms, pointing to putative causal variants and candidate genes, pathways and tissues for functional studies. Further, we define physiological correlates for insomnia symptoms and meaningful clinical links, including genetic overlap with RLS and a possible causal link with coronary artery disease. This work is supported by grants NIH F32DK102323, NIH 4T32HL007901, NIH R01DK107859, NIH R35 HL135818, MGH Research Scholar Fund, the Wellcome Investigator Award, UK MRC MC_UU_12013/5 and The University of Manchester Research Infrastructure Fund." @default.
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• W2788173172 date "2018-04-01" @default.
• W2788173172 modified "2023-10-18" @default.
• W2788173172 title "0015 Biological And Clinical Insights from Genetics of Insomnia Symptoms" @default.
• W2788173172 doi "https://doi.org/10.1093/sleep/zsy061.014" @default.
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