title: A population-based association study of candidate genes for depression and sleep disturbance.
abstract: The clinical manifestation of depression comprises a variety of symptoms, including early morning awakenings and fatigue, features also indicating disturbed sleep. The presence or absence of these symptoms may reflect differences in neurobiological processes leading to prolonged depression. Several neurobiological mechanisms have been indicated in the induction of depression, including disturbances in serotonergic and glutamatergic neurotransmission and in the action of the hypothalamic-pituitary-adrenal (HPA) axis. The same transmitters have also been linked to sleep regulation. We hypothesized that depression without simultaneous symptoms of disturbed sleep would partly have a different genetic background than depression with symptoms of disturbed sleep. We tested this hypothesis using a systematic population-based association study of 14 candidate genes related to depression and disturbed sleep. Association of genetic variants with either depression alone, depression with early morning awakenings, or depression with fatigue was investigated using permutation-based allelic association analysis of a sample of 1,654 adults recruited from Finland's population-based program. The major findings were associations of TPH2 (rs12229394) with depression accompanied by fatigue in women and CREB1 (rs11904814) with depression alone in men. We also found suggestive associations in women for GAD1, GRIA3, and BDNF with depression accompanied by fatigue, and for CRHR1 with depression accompanied by early morning awakenings. The results indicate sex-dependent and symptom-specific differences in the genetic background of depression. These differences may partially explain the broad spectrum of depressive symptoms, and their systematic monitoring could potentially be used for diagnostic purposes.
authors: Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.|Department of Physiology, University of Helsinki, Helsinki, Finland.|Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
authors: Siddheshwar
authors: S
authors: Utge
authors: Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.|Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
authors: Pia
authors: P
authors: Soronen
authors: Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
authors: Timo
authors: T
authors: Partonen
authors: Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors: Anu
authors: A
authors: Loukola
authors: Department of Health and Functional Capacity, Laboratory for Population Research, National Institute for Health and Welfare, Turku, Finland.
authors: Erkki
authors: E
authors: Kronholm
authors: Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.|Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
authors: Sami
authors: S
authors: Pirkola
authors: Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors: Emma
authors: E
authors: Nyman
authors: Department of Physiology, University of Helsinki, Helsinki, Finland.
authors: Tarja
authors: T
authors: Porkka-Heiskanen
authors: Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.|Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
authors: Tiina
authors: T
authors: Paunio
mesh_terms: D000328:Adult; D000483:Alleles; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity; D012737:Sex Factors; D012893:Sleep Wake Disorders / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase