Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways
| Autor: | Jansen, Philip R., Watanabe, Kyoko, Stringer, Sven, Skene, Nathan, Bryois, Julien, Hammerschlag, Anke R., de Leeuw, Christiaan A., Benjamins, Jeroen S., Muñoz-Manchado, Ana B., Nagel, Mats, Savage, Jeanne E., Tiemeier, Henning, White, Tonya, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Hinds, David A., Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Noblin, Elizabeth S., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Wilson, Catherine H., Tung, Joyce Y., Vacic, Vladimir, Wang, Xin, Sullivan, Patrick F., van der Sluis, Sophie, Polderman, Tinca J. C., Smit, August B., Hjerling-Leffler, Jens, van Someren, Eus J. W., Posthuma, Danielle |
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| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN), Academic Medical Center, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Integrative Neurophysiology, Human genetics, APH - Mental Health, Psychiatry, Amsterdam Reproduction & Development (AR&D), APH - Aging & Later Life, Child and Adolescent Psychiatry / Psychology |
| Rok vydání: | 2019 |
| Předmět: |
Male
Cell type Quantitative Trait Loci Disease Biology Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being Sleep Initiation and Maintenance Disorders Mendelian randomization Genetics Humans Genetic Predisposition to Disease Gene 030304 developmental biology Genetic association 0303 health sciences Middle Aged Heritability Phenotype Chromatin 3. Good health Expression quantitative trait loci Female Sleep 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Nature Genetics, 51, 394-403. Nature Publishing Group Nature genetics, 51(3), 394-403. Nature Publishing Group Nature Genetics, 51, 394. Nature Publishing Group Nature Genetics, 51(3), 394-403. Nature Publishing Group Nature Genetics The 23andMe Research Team 2019, ' Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways ', Nature Genetics, vol. 51, no. 3, pp. 394-403 . https://doi.org/10.1038/s41588-018-0333-3 the 23andMe Research Team 2019, ' Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways ', Nature Genetics, vol. 51, no. 3, pp. 394-403 . https://doi.org/10.1038/s41588-018-0333-3 |
| ISSN: | 1546-1718 1061-4036 |
| Popis: | Insomnia is the second most prevalent mental disorder, with no sufficient treatment available. Despite substantial heritability, insight into the associated genes and neurobiological pathways remains limited. Here, we use a large genetic association sample (n = 1,331,010) to detect novel loci and gain insight into the pathways, tissue and cell types involved in insomnia complaints. We identify 202 loci implicating 956 genes through positional, expression quantitative trait loci, and chromatin mapping. The meta-analysis explained 2.6% of the variance. We show gene set enrichments for the axonal part of neurons, cortical and subcortical tissues, and specific cell types, including striatal, hypothalamic, and claustrum neurons. We found considerable genetic correlations with psychiatric traits and sleep duration, and modest correlations with other sleep-related traits. Mendelian randomization identified the causal effects of insomnia on depression, diabetes, and cardiovascular disease, and the protective effects of educational attainment and intracranial volume. Our findings highlight key brain areas and cell types implicated in insomnia, and provide new treatment targets. |
| Databáze: | OpenAIRE |
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