title: Genome-wide association analysis of actigraphic sleep phenotypes in the LIFE Adult Study.
abstract: The genetic basis of sleep is still poorly understood. Despite the moderate to high heritability of sleep-related phenotypes, known genetic variants explain only a small proportion of the phenotypical variance. However, most previous studies were based solely upon self-report measures. The present study aimed to conduct the first genome-wide association (GWA) of actigraphic sleep phenotypes. The analyses included 956 middle- to older-aged subjects (40-79 years) from the LIFE Adult Study. The SenseWear Pro 3 Armband was used to collect 11 actigraphic parameters of night- and daytime sleep and three parameters of rest (lying down). The parameters comprised measures of sleep timing, quantity and quality. A total of 7 141 204 single nucleotide polymorphisms (SNPs) were analysed after imputation and quality control. We identified several variants below the significance threshold of P ≤ 5× 10-8(not corrected for analysis of multiple traits). The most significant was a hit near UFL1 associated with sleep efficiency on weekdays (P = 1.39 × 10-8). Further SNPs were close to significance, including an association between sleep latency and a variant in CSNK2A1 (P = 8.20 × 10-8), a gene known to be involved in the regulation of circadian rhythm. In summary, our GWAS identified novel candidate genes with biological plausibility being promising candidates for replication and further follow-up studies.
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.|Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.|Depression Research Centre, German Depression Foundation, Leipzig, Germany.
authors.forename: Janek
authors.initials: J
authors.lastname: Spada
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.|Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Universität Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Scholz
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.|Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Universität Leipzig, Leipzig, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Kirsten
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.|Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Hensch
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.|Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Universität Leipzig, Leipzig, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Horn
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.|Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.|Depression Research Centre, German Depression Foundation, Leipzig, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Jawinski
authors.affiliation: Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.|Depression Research Centre, German Depression Foundation, Leipzig, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Ulke
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.|Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Burkhardt
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wirkner
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.|Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Universität Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.|Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.|Depression Research Centre, German Depression Foundation, Leipzig, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hegerl
authors.affiliation: LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany.|Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.|Depression Research Centre, German Depression Foundation, Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sander
mesh_terms: D056044:Actigraphy; D000328:Adult; D000368:Aged; D047390:Casein Kinase II / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012146:Rest; D057566:Self Report; D012890:Sleep / Q000235:genetics* / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D044767:Ubiquitin-Protein Ligases; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II; C587954:UFL1 protein, human
keywords: affective disorders; genetics; napping; night-sleep; sleep duration