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A variant in orexin receptor-2 is associated with self-reported daytime sleepiness in the Japanese population

Journal of Human Genetics volume 67, pages 377–380 (2022)Cite this article

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Abstract

Excessive daytime sleepiness is characterized by a persistent feeling of having trouble staying awake, typically with inappropriate sleep episodes. Orexin (hypocretin) is a neuropeptide that regulates sleep-wake cycles and rapid eye movement sleep. Several large-scale genome-wide association studies (GWASs) in European populations have found genetic variants in orexin receptor-1 (OX1R) and -2 (OX2R) that are associated with sleep traits including daytime sleepiness. To identify genetic variants associated with daytime sleepiness, we performed an association study of genetic variants in prepro-orexin, OX1R, and OX2R in 14,329 Japanese individuals from the Tohoku Medical Megabank Project cohort. A genetic variant in OX2R was significantly associated with self-reported daytime sleepiness after Bonferroni correction (rs188018846: P = 8.4E−05). In addition, a missense variant in OX2R identified by the European GWASs showed a nominally significant association with daytime sleepiness in a Japanese population (p.Ile308Val, rs2653349: P = 0.044). Multiple genetic variants in OX2R can affect daytime sleepiness in general populations.

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Acknowledgements

This research was conducted using the ToMMo biobank resource under research number 2019-0110. The authors are deeply grateful to all participants in the present study. This study was supported by Grants-in-Aid for Scientific Research (B) (19H03588) and (C) (21K07534) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funder had no role in study design, data collection, analysis, the decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Taku Miyagawa, Mihoko Shimada, Yoshiko Honda, Tohru Kodama & Makoto Honda

  2. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Taku Miyagawa, Mihoko Shimada & Katsushi Tokunaga

  3. Genome Medical Science Project (Toyama), National Center for Global Health and Medicine, Tokyo, Japan

    Mihoko Shimada & Katsushi Tokunaga

  4. Koishikawa Tokyo Hospital, Institute of Neuropsychiatry, Tokyo, Japan

    Makoto Honda

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  1. Taku Miyagawa
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  2. Mihoko Shimada
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  3. Yoshiko Honda
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  4. Tohru Kodama
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  5. Katsushi Tokunaga
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Correspondence to Taku Miyagawa.

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MH has received consulting fees from Takeda Pharmaceutical Co. Ltd. The other authors declare no competing interests.

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Miyagawa, T., Shimada, M., Honda, Y. et al. A variant in orexin receptor-2 is associated with self-reported daytime sleepiness in the Japanese population. J Hum Genet 67, 377–380 (2022). https://doi.org/10.1038/s10038-022-01015-2

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  • DOI: https://doi.org/10.1038/s10038-022-01015-2

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