<br>PER2 的睡眠型遗传变异与人类内在昼夜节律周期相关。,Scientific Reports

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PER2 的睡眠型遗传变异与人类内在昼夜节律周期相关。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-03-29 , DOI: 10.1038/s41598-019-41712-1
Anne-Marie Chang _{1,

2,

3,

4} , Jeanne F Duffy _{2,

3} , Orfeu M Buxton _{1,

2,

3,

5} , Jacqueline M Lane _{4,

6} , Daniel Aeschbach _{2,

3,

7} , Clare Anderson _{2,

3,

8} , Andrew C Bjonnes _{4,

6} , Sean W Cain _{2,

3,

8} , Daniel A Cohen _{2,

3} , Timothy M Frayling ₉ , Joshua J Gooley _{2,

3,

10} , Samuel E Jones ₉ , Elizabeth B Klerman _{2,

3} , Steven W Lockley _{2,

3} , Mirjam Munch _{2,

3,

11} , Shantha M W Rajaratnam _{2,

3,

8} , Melanie Rueger _{2,

3} , Martin K Rutter _{12,

13} , Nayantara Santhi _{2,

3,

14} , Karine Scheuermaier _{2,

3,

15} , Eliza Van Reen _{2,

3,

16} , Michael N Weedon ₉ , Charles A Czeisler _{2,

3} , Frank A J L Scheer _{2,

3} , Richa Saxena _{2,

4,

6}

Affiliation

Department of Biobehavioral Health, Pennsylvania State University, University Park, Pennsylvania, 16802, USA.
Division of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, 02115, USA.
Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA.
Department of Social and Behavioral Sciences, Harvard Chan School of Public Health, Boston, Massachusetts, 02115, USA.
Department of Anesthesia, Critical Care and Pain Medicine and Center for Genomic Medicine; Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.
Department of Sleep and Human Factors Research, Institute of Aerospace Medicine, German Aerospace Center, Cologne, 51147, Germany.
Monash Institute of Cognitive and Clinical Neurosciences and School of Psychological Sciences, Monash University, Clayton, VIC, Australia.
Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.
Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
Sleep/Wake Research Centre, College of Health, Massey University, Wellington, New Zealand.
Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Manchester Diabetes Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Surrey Sleep Research Centre, University of Surrey, Guildford, UK.
Wits Sleep Laboratory, Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.

PERIOD2（PER2）基因是生物钟的核心分子组成部分，在日常节律的产生和维持中发挥着重要作用。 Rs35333999 是欧洲人群中常见的 PER2 错义变体，已被证明与较晚的时间型相关。计时型与生物和行为活动的时间安排有关，包括我们何时睡觉、吃饭和运动，而后来的计时型与较长的内在昼夜节律周期（周期长度）相关，这是昼夜节律系统的基本属性。因此，我们测试了这种 PER2 变体是否与昼夜节律周期相关，并发现与根据强制去同步协议（内在昼夜节律评估的“金标准”）测量的更长的内在昼夜节律周期显着相关。当基于核心体温或血浆褪黑激素测量结果进行测定时，与非携带者相比，次要等位基因 (T) 携带者表现出明显更长的昼夜节律周期（分别延长 12 分钟和 11 分钟；约占个体间差异的 7%））。这些发现为个体间生物钟差异提供了可能的潜在生物学机制，并支持 PER2 在人类昼夜节律计时系统中的核心作用。

"点击查看英文标题和摘要"

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 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.

更新日期：2019-03-29

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