ArticleDiabetes2016
Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology.
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Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54citing papers in PubMed
7.4field-weighted citation impact, top 2% of its field
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Who cites it
54 citing papers in PubMed, 89 citations in OpenAlex.
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- The causal relationship between bacterial pneumonia and diabetes: a two-sample mendelian randomization study.Islets · 2024Article
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- Blue Light and Temperature Actigraphy Measures Predicting Metabolic Health Are Linked to Melatonin Receptor Polymorphism.Biology · 2023Article
- The melatonin receptor 1B gene links circadian rhythms and type 2 diabetes mellitus: an evolutionary story.Annals of medicine · 2023Review
- Myocardial Infarction Susceptibility and theInternational journal of molecular sciences · 2023Article
- Scalable mixed model methods for set-based association studies on large-scale categorical data analysis and its application to exome-sequencing data in UK Biobank.American journal of human genetics · 2023Article
- Role of Melatonin in Daily Variations of Plasma Insulin Level and Pancreatic Clock Gene Expression in Chick Exposed to Monochromatic Light.International journal of molecular sciences · 2023Article
- The circadian rhythm: an influential soundtrack in the diabetes story.Frontiers in endocrinology · 2023Review
- Genetics of circadian rhythms and sleep in human health and disease.Nature reviews. Genetics · 2023Review
- Time for Exercise? Exercise and Its Influence on the Skeletal Muscle Clock.Journal of biological rhythms · 2022Article
- The role of MTNR1B polymorphism on circadian rhythm-related cancer: A UK Biobank cohort study.International journal of cancer · 2022Article
- Interaction of night shift work with polymorphism in melatonin receptor 1B gene on incident stroke.Scandinavian journal of work, environment & health · 2022Article
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Authors and funding
31 authors at 11 institutions in 3 countries.
Jacqueline M LaneCenter for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA Program in Medical and Population Genetics, Broad Institute, Cambridge, MA Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA.
Anne-Marie ChangProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA Department of Biobehavioral Health, Pennsylvania State University, University Park, PA.
Andrew C BjonnesCenter for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA Program in Medical and Population Genetics, Broad Institute, Cambridge, MA Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA.
Daniel AeschbachDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany.
Clare AndersonDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Brian E CadeDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Sean W CainDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Charles A CzeislerDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Sina A GharibComputational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Department of Medicine, University of Washington, Seattle, WA.
Joshua J GooleyDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Daniel J GottliebDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Struan F A GrantPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA.
Elizabeth B KlermanDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Diane S LauderdaleDepartment of Health Studies, The University of Chicago, Chicago, IL.
Steven W LockleyDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.
Miriam MunchDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Sanjay PatelDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Naresh M PunjabiDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD.
Shanthakumar M W RajaratnamDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Melanie RuegerDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Melissa A St HilaireDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Nayantara SanthiDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Karin ScheuermaierDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Eliza Van ReenDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Phyllis C ZeeThe Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL.
Steven A SheaDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Jeanne F DuffyDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Orfeu M BuxtonDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA Department of Biobehavioral Health, Pennsylvania State University, University Park, PA Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA.
Susan RedlineDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Frank A J L ScheerDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Richa SaxenaCenter for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA Program in Medical and Population Genetics, Broad Institute, Cambridge, MA Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA rsaxena@broadinstitute.org.
Circadian (United States) · USHarvard University · USBrigham and Women's Hospital · USBroad Institute · USCenter for Human Genetics · USJohns Hopkins University · USMonash University · AUNorthwestern University · USUniversity of Chicago · USUniversity of Pennsylvania · USUniversity of Washington · US
Funding
Zoledronic Acid in Treatment of Osteoporosis in PostmenoM01RR002635 · NCRR · BRIGHAM AND WOMEN'S HOSPITAL · PI WILLIAMS, GORDON H · 1985 to 2008
$48.4MTRANSPLANTATION ANALYSIS OF CIRCADIAN RHYTHMS AND AGINGP01AG009975 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI SAPER, CLIFFORD B · 1991 to 2018
$23.1MTRAINING IN SLEEP, CIRCADIAN &RESPIRATORY NEUROBIOLOGYT32HL007901 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Charles A Czeisler · 1998 to 2026
$18.5MStatistical Methods for Analysis of Massive Genetic and Genomic Data in Cancer ResearchR35CA197449 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI XIHONG LIN · 2015 to 2026
$10.9MASSOCIATION OF SLEEP DISORDERS WITH CARDIOVASCULAR HEALTH ACROSS ETHNIC GROUPSR01HL098433 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI REDLINE, SUSAN S. · 2010 to 2015
$8.2MTREATMENT 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
$4.4MTreatment of Circadian Disruption from Shiftwork in Older AdultsR01AG044416 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI DUFFY, JEANNE F · 2013 to 2022
$4.3MSleep 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
$2.8MTHE SLEEP HEART HEALTH STUDY: READING CENTER APPLICATIONU01HL063463 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI REDLINE, SUSAN S. · 1999 to 2007
$2.8MAdaptation of Circadian Responses to Light TreatmentR01HL077453 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DUFFY, JEANNE F · 2004 to 2010
$2.6MNCCIH NIH HHS R21 AT002571NCI NIH HHS R35 CA197449NCRR NIH HHS M01 RR002635NHLBI NIH HHS K01 HL115458NHLBI 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 HL098433NHLBI NIH HHS R01 HL113338NHLBI NIH HHS R01 HL114088NHLBI NIH HHS R01 HL118601NHLBI NIH HHS R21 HL121728NHLBI NIH HHS RC2 HL101340NHLBI NIH HHS T32 HL007901NHLBI NIH HHS U01 HL053916NHLBI NIH HHS U01 HL053934NHLBI NIH HHS U01 HL053937NHLBI NIH HHS U01 HL053941NHLBI NIH HHS U01 HL063429NHLBI NIH HHS U01 HL063463NIA NIH HHS P01 AG009975NIA NIH HHS R01 AG006072NIA NIH HHS R01 AG044416NIDDK NIH HHS F32 DK102323NIDDK NIH HHS R01 DK099512NIDDK NIH HHS R21 DK089378NIMH NIH HHS R01 MH045130NINDS NIH HHS R01 NS054277
Abstract
The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive in-laboratory protocols (n = 58-96) or cross-sectional studies with sleep quantity and quality and timing measures from self-report (n = 4,307-10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021). In the in-laboratory studies, we found a significant association with a substantially longer duration of elevated melatonin levels (41 min) and delayed circadian phase of dim-light melatonin offset (1.37 h), partially mediated through delayed offset of melatonin synthesis. Furthermore, increased T2D risk in MTNR1B risk allele carriers was more pronounced in early risers versus late risers as determined by 7 days of actigraphy. Our results provide the surprising insight that the MTNR1B risk allele influences dynamics of melatonin secretion, generating a novel hypothesis that the MTNR1B risk allele may extend the duration of endogenous melatonin production later into the morning and that early waking may magnify the diabetes risk conferred by the risk allele.
Indexed as
AdultAllelesBlood GlucoseCircadian RhythmCross-Sectional StudiesDiabetes Mellitus, Type 2FastingFemaleGenetic VariationHumansMaleMelatoninPhenotypeReceptor, Melatonin, MT2Risk FactorsSleepBlood GlucoseMelatoninMTNR1B protein, humanReceptor, Melatonin, MT2
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