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Nightmares share strong genetic risk with sleep and psychiatric disorders

Hanna M Ollila, Nasa Sinnott-Armstrong, Katri Kantojärvi, Teemu Palviainen, Anita Pandit, Robin Rong, Kati Kristiansson, Nils Sandman, Katja Valli, Christer Hublin, Jaakko Kaprio, Richa Saxena, Tiina Paunio
doi: https://doi.org/10.1101/836452
Hanna M Ollila
1Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
2Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA., USA
3Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA., USA and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
4Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA
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  • For correspondence: Tiina.paunio@thl.fi rsaxena@broadinstitute.org hanna.m.ollila@helsinki.fi
Nasa Sinnott-Armstrong
4Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA
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Katri Kantojärvi
5Genomics and Biomarkers Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
6Department of Psychiatry and SleepWell Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
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Teemu Palviainen
1Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
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Anita Pandit
7Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
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Robin Rong
7Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
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Kati Kristiansson
5Genomics and Biomarkers Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
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Nils Sandman
8Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center, University of Turku, Turku, Finland
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Katja Valli
8Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center, University of Turku, Turku, Finland
9Department of Cognitive Neuroscience and Philosophy, University of Skövde, Skövde, Sweden
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Christer Hublin
10Finnish Institute of Occupational Health, Helsinki, Finland
11Department of Public Health, University of Helsinki, Helsinki, Finland
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Jaakko Kaprio
1Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
11Department of Public Health, University of Helsinki, Helsinki, Finland
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Richa Saxena
3Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA., USA and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
12Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
13Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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  • For correspondence: Tiina.paunio@thl.fi rsaxena@broadinstitute.org hanna.m.ollila@helsinki.fi
Tiina Paunio
5Genomics and Biomarkers Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
6Department of Psychiatry and SleepWell Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
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  • For correspondence: Tiina.paunio@thl.fi rsaxena@broadinstitute.org hanna.m.ollila@helsinki.fi
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ABSTRACT

Nightmares are vivid, extended and extremely dysphoric dreams that awaken the dreamer. Twin studies indicate that nightmare frequency has a heritability between 36 and 51% providing evidence for genetic factors underlying predisposition to nightmares. Furthermore, while cross-sectional epidemiological findings suggest that heavy alcohol usage, traumatic experiences and psychiatric diseases associate with nightmares, the causal relationships between these conditions and nightmares have remained unknown. To examine the biological mechanisms behind nightmares, we performed a genome-wide association study in 28,596 individuals from Finland and the United States. We identified individual genetic variants that predispose to nightmares near MYOF (rs701873, p=2.18e-8) and PTPRJ (rs11039471,p=3.7e-8), a gene previously associated with sleep duration. We found a strong genetic correlation between the frequency of nightmares and traits related to personality and psychiatric disorders; neuroticism (rg=0.59, p=8e-7), post-traumatic stress disorder (PTSD) (rg=0.58, p=0.004) as well as major depressive disorder (rg=0.68, p=7e-4), and sleep traits; and daytime sleepiness (rg=0.62, p=1e-6) and insomnia (rg=0.50, p=1.87e-5). Analysis of directionality using mendelian randomization showed a significant effect from feelings of fed-up (p=0.001), nervous (p=0.004) and miserableness (p=0.0045) to nightmares with no evidence of pleiotropy and no evidence of nightmares predisposing to psychiatric or psychological problems. Our findings suggest that nightmares are caused by unique genetic risk factors, and here we identify the first individual genetic associations. In addition, a substantial effect on nightmares is conveyed through underlying psychological and sleep problems, with psychological problems being causal for nightmares.

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Posted November 09, 2019.
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Nightmares share strong genetic risk with sleep and psychiatric disorders
Hanna M Ollila, Nasa Sinnott-Armstrong, Katri Kantojärvi, Teemu Palviainen, Anita Pandit, Robin Rong, Kati Kristiansson, Nils Sandman, Katja Valli, Christer Hublin, Jaakko Kaprio, Richa Saxena, Tiina Paunio
bioRxiv 836452; doi: https://doi.org/10.1101/836452
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Nightmares share strong genetic risk with sleep and psychiatric disorders
Hanna M Ollila, Nasa Sinnott-Armstrong, Katri Kantojärvi, Teemu Palviainen, Anita Pandit, Robin Rong, Kati Kristiansson, Nils Sandman, Katja Valli, Christer Hublin, Jaakko Kaprio, Richa Saxena, Tiina Paunio
bioRxiv 836452; doi: https://doi.org/10.1101/836452

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