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Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans

The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to...

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Autores principales: Chang, Anne-Marie, Duffy, Jeanne F., Buxton, Orfeu M., Lane, Jacqueline M., Aeschbach, Daniel, Anderson, Clare, Bjonnes, Andrew C., Cain, Sean W., Cohen, Daniel A., Frayling, Timothy M., Gooley, Joshua J., Jones, Samuel E., Klerman, Elizabeth B., Lockley, Steven W., Munch, Mirjam, Rajaratnam, Shantha M. W., Rueger, Melanie, Rutter, Martin K., Santhi, Nayantara, Scheuermaier, Karine, Van Reen, Eliza, Weedon, Michael N., Czeisler, Charles A., Scheer, Frank A. J. L., Saxena, Richa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440993/
https://www.ncbi.nlm.nih.gov/pubmed/30926824
http://dx.doi.org/10.1038/s41598-019-41712-1
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author Chang, Anne-Marie
Duffy, Jeanne F.
Buxton, Orfeu M.
Lane, Jacqueline M.
Aeschbach, Daniel
Anderson, Clare
Bjonnes, Andrew C.
Cain, Sean W.
Cohen, Daniel A.
Frayling, Timothy M.
Gooley, Joshua J.
Jones, Samuel E.
Klerman, Elizabeth B.
Lockley, Steven W.
Munch, Mirjam
Rajaratnam, Shantha M. W.
Rueger, Melanie
Rutter, Martin K.
Santhi, Nayantara
Scheuermaier, Karine
Van Reen, Eliza
Weedon, Michael N.
Czeisler, Charles A.
Scheer, Frank A. J. L.
Saxena, Richa
author_facet Chang, Anne-Marie
Duffy, Jeanne F.
Buxton, Orfeu M.
Lane, Jacqueline M.
Aeschbach, Daniel
Anderson, Clare
Bjonnes, Andrew C.
Cain, Sean W.
Cohen, Daniel A.
Frayling, Timothy M.
Gooley, Joshua J.
Jones, Samuel E.
Klerman, Elizabeth B.
Lockley, Steven W.
Munch, Mirjam
Rajaratnam, Shantha M. W.
Rueger, Melanie
Rutter, Martin K.
Santhi, Nayantara
Scheuermaier, Karine
Van Reen, Eliza
Weedon, Michael N.
Czeisler, Charles A.
Scheer, Frank A. J. L.
Saxena, Richa
author_sort Chang, Anne-Marie
collection PubMed
description The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the ‘gold standard’ for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system.
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spelling pubmed-64409932019-04-04 Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans Chang, Anne-Marie Duffy, Jeanne F. Buxton, Orfeu M. Lane, Jacqueline M. Aeschbach, Daniel Anderson, Clare Bjonnes, Andrew C. Cain, Sean W. Cohen, Daniel A. Frayling, Timothy M. Gooley, Joshua J. Jones, Samuel E. Klerman, Elizabeth B. Lockley, Steven W. Munch, Mirjam Rajaratnam, Shantha M. W. Rueger, Melanie Rutter, Martin K. Santhi, Nayantara Scheuermaier, Karine Van Reen, Eliza Weedon, Michael N. Czeisler, Charles A. Scheer, Frank A. J. L. Saxena, Richa Sci Rep Article The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the ‘gold standard’ for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system. Nature Publishing Group UK 2019-03-29 /pmc/articles/PMC6440993/ /pubmed/30926824 http://dx.doi.org/10.1038/s41598-019-41712-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chang, Anne-Marie
Duffy, Jeanne F.
Buxton, Orfeu M.
Lane, Jacqueline M.
Aeschbach, Daniel
Anderson, Clare
Bjonnes, Andrew C.
Cain, Sean W.
Cohen, Daniel A.
Frayling, Timothy M.
Gooley, Joshua J.
Jones, Samuel E.
Klerman, Elizabeth B.
Lockley, Steven W.
Munch, Mirjam
Rajaratnam, Shantha M. W.
Rueger, Melanie
Rutter, Martin K.
Santhi, Nayantara
Scheuermaier, Karine
Van Reen, Eliza
Weedon, Michael N.
Czeisler, Charles A.
Scheer, Frank A. J. L.
Saxena, Richa
Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans
title Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans
title_full Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans
title_fullStr Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans
title_full_unstemmed Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans
title_short Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans
title_sort chronotype genetic variant in per2 is associated with intrinsic circadian period in humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440993/
https://www.ncbi.nlm.nih.gov/pubmed/30926824
http://dx.doi.org/10.1038/s41598-019-41712-1
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