ArticleScientific reports2019
Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans.
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Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Influence of Chronotype on Cycling Performance in Simulated 20-km Time Trials-A Pilot Study.Journal of sleep research · 2026Article
- Morning Larks and Night Owls: Considering Chronotype in Evaluation of Patients with Pulmonary Hypertension.Annals of the American Thoracic Society · 2026Article
- Sex-specific sleep profiles in Spanish adults: cross-sectional actigraphy-PSQI study with cluster analysis in Salamanca and Ávila.BMJ open · 2025Observational
- Clinical Implication of Time of Ischaemic Stroke Among Post-Stroke Survivors from Eastern India: A Circadian Perspective.Neuromolecular medicine · 2024Article
- Using Polygenic Scores for Circadian Rhythms to Predict Wellbeing, Depressive Symptoms, Chronotype, and Health.Journal of biological rhythms · 2024Article
- Circadian regulation of liver metabolism: experimental approaches in human, rodent, and cellular models.American journal of physiology. Cell physiology · 2023Review
- The relations between chronotype, stressful life events, and impulsivity in the Adolescent Brain Cognitive Development (ABCD) study.Journal of psychiatric research · 2023Article
- Human-Centric Lighting Research and Policy in the Melanopsin Age.Policy insights from the behavioral and brain sciences · 2023Article
- Desynchronizing the sleep---wake cycle from circadian timing to assess their separate contributions to physiology and behaviour and to estimate intrinsic circadian period.Nature protocols · 2023Review
- Genetics of circadian rhythms and sleep in human health and disease.Nature reviews. Genetics · 2023Review
- Delayed sleep-wake phase disorder and its related sleep behaviors in the young generation.Frontiers in psychiatry · 2023Review
- Chronotype Differences in Body Composition, Dietary Intake and Eating Behavior Outcomes: A Scoping Systematic Review.Advances in nutrition (Bethesda, Md.) · 2022Article
- Keeping an eye on circadian time in clinical research and medicine.Clinical and translational medicine · 2022Review
- The impact of lithium on circadian rhythms and implications for bipolar disorder pharmacotherapy.Neuroscience letters · 2022Review
- Spontaneous Recovery of Circadian Organization in Mice Lacking a Core Component of the Molecular Clockwork.Journal of biological rhythms · 2022Article
- Circadian Rhythm and Nuclear Receptors.Advances in experimental medicine and biology · 2022Article
- Investigation of gene-gene interactions of clock genes for chronotype in a healthy Korean population.Genomics & informatics · 2020Article
- Genetics of the human circadian clock and sleep homeostat.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Review
- Circadian Clock Protein PERIOD2 Suppresses the PI3K/Akt Pathway and Promotes Cisplatin Sensitivity in Ovarian Cancer.Cancer management and research · 2020Article
- A missense variant in PER2 is associated with delayed sleep-wake phase disorder in a Japanese population.Journal of human genetics · 2019Article
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Authors and funding
25 authors.
Anne-Marie ChangDepartment of Biobehavioral Health, Pennsylvania State University, University Park, Pennsylvania, 16802, USA. amchang@psu.edu.
Jeanne F DuffyDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Orfeu M BuxtonDepartment of Biobehavioral Health, Pennsylvania State University, University Park, Pennsylvania, 16802, USA.ORCID http://orcid.org/0000-0001-5057-633X
Jacqueline M LaneMedical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA.
Daniel AeschbachDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Clare AndersonDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Andrew C BjonnesMedical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA.
Sean W CainDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.ORCID http://orcid.org/0000-0002-8385-1550
Daniel A CohenDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Timothy M FraylingGenetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.
Joshua J GooleyDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Samuel E JonesGenetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.ORCID http://orcid.org/0000-0003-0153-922X
Elizabeth B KlermanDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Steven W LockleyDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Mirjam MunchDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Shantha M W RajaratnamDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Melanie RuegerDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Martin K RutterDivision of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Nayantara SanthiDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Karine ScheuermaierDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Eliza Van ReenDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Michael N WeedonGenetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.
Charles A CzeislerDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Frank A J L ScheerDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA. fscheer@bwh.harvard.edu.ORCID http://orcid.org/0000-0002-2014-7582
Richa SaxenaDivision of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.ORCID http://orcid.org/0000-0003-2233-1065
Funding
Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2MTRANSPLANTATION ANALYSIS OF CIRCADIAN RHYTHMS AND AGINGP01AG009975 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI KLERMAN, ELIZABETH B. · 1991 to 2018
$23.1MTRAINING IN SLEEP, CIRCADIAN &RESPIRATORY NEUROBIOLOGYT32HL007901 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Charles A Czeisler · 1998 to 2026
$18.5MTREATMENT OF CIRCADIAN SLEEP DISORDERS WITH BRIGHT LIGHTR01MH045130 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI LOCKLEY, STEVEN W · 1989 to 2010
$4.9MLeveraging Family Data to Identify Genetic Variants for Sleep ApneaR01HL113338 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIN, XIHONG, REDLINE, SUSAN S. · 2012 to 2016
$4.4MRole of Meal Timing in Efficacy of Bariatric Surgery in Obese IndividualsR01HL140574 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SCHEER, FRANK A, TAVAKKOLI, ALI · 2017 to 2023
$4.2MGenetics of chronotype and impact on metabolic diseaseR01DK107859 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Richa Saxena · 2016 to 2026
$4.0MMelatonin and Receptor Gene Variant: Linking Circadian System and Type 2 DiabetesR01DK102696 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI SAXENA, RICHA, SCHEER, FRANK A · 2015 to 2019
$3.8MImpact of Malatonin, Food Timing and Receptor Variant on Type 2 Diabetes RiskR01DK105072 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI SAXENA, RICHA, SCHEER, FRANK A · 2016 to 2020
$3.2MSleep duration required to restore performance during chronic sleep restrictionR01HL114088 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI KLERMAN, ELIZABETH B. · 2012 to 2015
$3.1MMeal Time Effects on Metabolic Health.R01DK099512 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI SCHEER, FRANK A · 2014 to 2017
$2.8MAdaptation of Circadian Responses to Light TreatmentR01HL077453 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DUFFY, JEANNE F · 2004 to 2010
$2.6MMedical Research Council MR/P012167/1NCATS NIH HHS UL1 TR001102NCCIH NIH HHS R21 AT002571NHLBI NIH HHS F32 HL078360NHLBI NIH HHS K01 HL115458NHLBI NIH HHS K01 HL136884NHLBI NIH HHS K24 HL105664NHLBI NIH HHS R01 HL077399NHLBI NIH HHS R01 HL077453NHLBI NIH HHS R01 HL080978NHLBI NIH HHS R01 HL093279NHLBI NIH HHS R01 HL094654NHLBI NIH HHS R01 HL094806NHLBI NIH HHS R01 HL113338NHLBI NIH HHS R01 HL114088NHLBI NIH HHS R01 HL118601NHLBI NIH HHS R01 HL140574NHLBI NIH HHS R21 HL121728NHLBI NIH HHS T32 HL007901NIA NIH HHS F32 AG031690NIA NIH HHS P01 AG009975NIA NIH HHS R01 AG006072NICHD NIH HHS R21 HD086392NIDDK NIH HHS F32 DK102323NIDDK NIH HHS R01 DK099512NIDDK NIH HHS R01 DK102696NIDDK NIH HHS R01 DK105072NIDDK NIH HHS R01 DK107859NIDDK NIH HHS R21 DK089378NIGMS NIH HHS R01 GM105018NIMH NIH HHS R01 MH045130NINDS NIH HHS R01 NS054277
Abstract
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.
Indexed as
Genetic VariationAdultAgedAllelesCircadian ClocksCircadian RhythmFemaleGenotypeHumansMaleMiddle AgedPeriod Circadian ProteinsPhenotypePolymorphism, Single NucleotidePER2 protein, humanPeriod Circadian Proteins
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