Evidence map›Paper›PMID 35670608›Full record

SynthesisSleep2023

The genetic etiology of periodic limb movement in sleep.

Jacob L Edelson, Logan D Schneider, David Amar, Andreas Brink-Kjaer, Katie L Cederberg, Zoltán Kutalik, Erika W Hagen, Paul E Peppard, Priscila Farias Tempaku, Sergio Tufik and 12 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Sleep, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Evo-devo applied to sleep research: an approach whose time has come.Sleep advances : a journal of the Sleep Research Society · 2024
    Review
  6. Article
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 9 institutions in 4 countries.

Jacob L EdelsonDepartment of Biomedical Data Sciences, Stanford University School of Medicine, Palo Alto, CA 94603, USA.
Logan D SchneiderStanford/VA Alzheimer's Research Center, Palo Alto, CA 94603, USA.
David AmarStanford Department of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA 94603, USA.
Andreas Brink-KjaerStanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Palo Alto, CA 94603, USA.
Katie L CederbergStanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Palo Alto, CA 94603, USA.ORCID 0000-0001-5693-9293
Zoltán KutalikUniversity Center for Primary Care and Public Health, University of Lausanne, Lausanne 1010, Switzerland.
Erika W HagenUniversity of Wisconsin-Madison, School of Medicine and Public Health, Department of Population Health Sciences, Madison, WI 53726, USA.
Paul E PeppardUniversity of Wisconsin-Madison, School of Medicine and Public Health, Department of Population Health Sciences, Madison, WI 53726, USA.
Priscila Farias TempakuDepartment of Psychobiology, Universidade Federal de São Paulo, São Paulo 04021002, Brazil.
Sergio TufikDepartment of Psychobiology, Universidade Federal de São Paulo, São Paulo 04021002, Brazil.
Daniel S EvansCalifornia Pacific Medical Center, Research Institute, San Francisco, CA 94107, USA.
Katie StoneCalifornia Pacific Medical Center, Research Institute, San Francisco, CA 94107, USA.
Greg TranahCalifornia Pacific Medical Center, Research Institute, San Francisco, CA 94107, USA.
Brian CadeDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA 102115, USA.ORCID 0000-0003-1424-0673
Susan RedlineDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA 102115, USA.
Jose Haba-RubioDepartment of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne 1011, Switzerland.
Raphael HeinzerDepartment of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne 1011, Switzerland.
Pedro Marques-VidalDepartment of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne 1011, Switzerland.ORCID 0000-0002-4548-8500
Peter VollenweiderDepartment of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne 1011, Switzerland.ORCID 0000-0002-0765-896X
Juliane WinkelmannInstitute of Neurogenomics, Helmholtz Center Munich (HMGU) Technical University of Munich, 81675 Munich, Germany.
James ZouDepartment of Biomedical Data Sciences, Stanford University School of Medicine, Palo Alto, CA 94603, USA.
Emmanuel MignotStanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Palo Alto, CA 94603, USA.
Stanford University · USUniversity of Lausanne · CHBrigham and Women's Hospital · USCalifornia Pacific Medical Center · USUniversidade Federal de São Paulo · BRUniversity of Wisconsin–Madison · USHelmholtz Zentrum München · DESIB Swiss Institute of Bioinformatics · CHUniversity of California, San Francisco · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
INSTITUTIONAL CTSA (UW-MADISON): CLINICAL TRIALSUL1RR025011 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2007 to 2011
$29.5M
Oregon Clinical and Translational Research InstituteUL1TR000128 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$28.7M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
SUBCLINICAL CARDIOVASCULAR DISEASE COORDINATING CENTERN01HC95159 · NHLBI · UNIVERSITY OF WASHINGTON · PI KRONMAL, RICHARD A · 2007 to 2014
$19.6M
EPIDEMIOLOGY OF SLEEP-DISORDERED BREATHING IN ADULTSR01HL062252 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI PEPPARD, PAUL E · 1999 to 2013
$14.1M
Outcomes of Sleep Disorders in Older MenR01HL071194 · NHLBI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI STONE, KATIE L · 2003 to 2013
$12.2M
Osteoporotic Fractures in Men (MrOS) - San Francisco Coordinating CenterU01AR066160 · NIAMS · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · PI CUMMINGS, STEVEN RON · 2013 to 2017
$9.3M
SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTERN01HC95160 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL · 2007 to 2015
$7.7M
Phenotypic and Molecular Signatures for Sleep Apnea and Related MorbiditiesR35HL135818 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI REDLINE, SUSAN S. · 2017 to 2023
$7.2M
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6 · The paper itself

Abstract

STUDY

objectivesPeriodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects.

methodsThe MrOS study and Wisconsin Sleep Cohort Study (N = 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization.

resultsWe found 2 independent loci were significantly associated with PLMS: rs113851554 (p = 3.51 × 10-12, β = 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14); and rs9369062 (p = 3.06 × 10-22, β = 0.2093), a SNP located in the intron region of BTBD9 (6p12); both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS.

conclusionsBecause PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings.

Indexed as

Restless Legs SyndromeSleep Initiation and Maintenance DisordersCohort StudiesGenome-Wide Association StudyHumansMovementSleepgenome-wide association studyMendelian randomizationperiodic limb movementsrestless leg syndrome

Identifiers

PMID35670608
PMCPMC10091093
OpenAlexW4281638315

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.