title: Mitochondrial DNA Copy Number in Sleep Duration Discordant Monozygotic Twins.
abstract: OBJECTIVE
  Mitochondrial DNA (mtDNA) copy number is an important component of mitochondrial function and varies with age, disease, and environmental factors. We aimed to determine whether mtDNA copy number varies with habitual differences in sleep duration within pairs of monozygotic twins.
  
  
  METHODS
  Academic clinical research center.
  
  
  METHODS
  15 sleep duration discordant monozygotic twin pairs (30 twins, 80% female; mean age 42.1 years [SD 15.0]).
  
  
  METHODS
  Sleep duration was phenotyped with wrist actigraphy. Each twin pair included a "normal" (7-9 h/24) and "short" (< 7 h/24) sleeping twin. Fasting peripheral blood leukocyte DNA was assessed for mtDNA copy number via the n-fold difference between qPCR measured mtDNA and nuclear DNA creating an mtDNA measure without absolute units. We used generalized estimating equation linear regression models accounting for the correlated data structure to assess within-pair effects of sleep duration on mtDNA copy number.
  
  
  RESULTS
  Mean within-pair sleep duration difference per 24 hours was 94.3 minutes (SD 62.6 min). We found reduced sleep duration (β = 0.06; 95% CI 0.004, 0.12; P < 0.05) and sleep efficiency (β = 0.51; 95% CI 0.06, 0.95; P < 0.05) were significantly associated with reduced mtDNA copy number within twin pairs. Thus every 1-minute decrease in actigraphy-defined sleep duration was associated with a decrease in mtDNA copy number of 0.06. Likewise, a 1% decrease in actigraphy-defined sleep efficiency was associated with a decrease in mtDNA copy number of 0.51.
  
  
  CONCLUSIONS
  Reduced sleep duration and sleep efficiency were associated with reduced mitochondrial DNA copy number in sleep duration discordant monozygotic twins offering a potential mechanism whereby short sleep impairs health and longevity through mitochondrial stress.
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA.|Department of Pediatrics, University of Washington, Seattle, WA.
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Wrede
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology Unit, Institute of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: Jonas
authors.initials: J
authors.lastname: Mengel-From
authors.affiliation: Departments of Epidemiology and Medicine, University of Washington, Seattle, WA.|University of Washington Twin Registry, Seattle, WA.
authors.forename: Dedra
authors.initials: D
authors.lastname: Buchwald
authors.affiliation: Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA.|Center for Research on the Management of Sleep Disturbances, University of Washington, Seattle, WA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Vitiello
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bamshad
authors.affiliation: Departments of Epidemiology and Medicine, University of Washington, Seattle, WA.|University of Washington Twin Registry, Seattle, WA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Noonan
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology Unit, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology Unit, Institute of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.|Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA.|University of Washington Twin Registry, Seattle, WA.|Center for Research on the Management of Sleep Disturbances, University of Washington, Seattle, WA.
authors.forename: Nathaniel F
authors.initials: NF
authors.lastname: Watson
mesh_terms: D056044:Actigraphy; D000328:Adult; D000368:Aged; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012890:Sleep / Q000235:genetics* / Q000502:physiology*; D013997:Time Factors; D014430:Twins, Monozygotic / Q000235:genetics*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial
keywords: copy number; mitochondrial DNA; sleep discordance; sleep duration; twins