title: Shared genetic background for regulation of mood and sleep: association of GRIA3 with sleep duration in healthy Finnish women.
abstract: OBJECTIVE
  Sleeping 7 to 8 hours per night appears to be optimal, since both shorter and longer sleep times are related to increased morbidity and mortality. Depressive disorder is almost invariably accompanied by disturbed sleep, leading to decreased sleep duration, and disturbed sleep may be a precipitating factor in the initiation of depressive illness. Here, we examined whether, in healthy individuals, sleep duration is associated with genes that we earlier found to be associated with depressive disorder.
  
  
  METHODS
  Population-based molecular genetic study.
  
  
  METHODS
  Regression analysis of 23 risk variants for depressive disorder from 12 genes to sleep duration in healthy individuals.
  
  
  METHODS
  Three thousand, one hundred, forty-seven individuals (25-75 y) from population-based Health 2000 and FINRISK 2007 samples.
  
  
  RESULTS
  We found a significant association of rs687577 from GRIA3 on the X-chromosome with sleep duration in women (permutation-based corrected empirical P=0.00001, β=0.27; Bonferroni corrected P=0.0052; f=0.11). The frequency of C/C genotype previously found to increase risk for depression in women was highest among those who slept for 8 hours or less in all age groups younger than 70 years. Its frequency decreased with the lengthening of sleep duration, and those who slept for 9 to 10 hours showed a higher frequency of C/A or A/A genotypes, when compared with the midrange sleepers (7-8 hours) (permutation-based corrected empirical P=0.0003, OR=1.81).
  
  
  CONCLUSIONS
  The GRIA3 polymorphism that was previously found to be associated with depressive disorder in women showed an association with sleep duration in healthy women. Mood disorders and short sleep may share a common genetic background and biologic mechanisms that involve glutamatergic neurotransmission.
authors.affiliation: Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Siddheshwar
authors.initials: S
authors.lastname: Utge
authors.forename: Erkki
authors.initials: E
authors.lastname: Kronholm
authors.forename: Timo
authors.initials: T
authors.lastname: Partonen
authors.forename: Pia
authors.initials: P
authors.lastname: Soronen
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Ollila
authors.forename: Anu
authors.initials: A
authors.lastname: Loukola
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Tarja
authors.initials: T
authors.lastname: Porkka-Heiskanen
authors.forename: Tiina
authors.initials: T
authors.lastname: Paunio
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D005387:Finland; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018091:Receptors, AMPA / Q000235:genetics* / Q000502:physiology; D012737:Sex Factors; D012890:Sleep / Q000235:genetics*
chemical_list: D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3