Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.

Disturbances in the circadian pacemaker system are commonly found in individuals with depression and sleep-related problems. We hypothesized that some of the canonical circadian clock genes would be associated with depression accompanied by signs of disturbed sleep, early morning awakening, or dayti...

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Autores principales: Siddheshwar J Utge, Pia Soronen, Anu Loukola, Erkki Kronholm, Hanna M Ollila, Sami Pirkola, Tarja Porkka-Heiskanen, Timo Partonen, Tiina Paunio
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Publicado: Public Library of Science (PLoS) 2010
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spelling oai:doaj.org-article:c574ebcdbab043a18d593cd3ff463f922021-11-25T06:25:44ZSystematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.1932-620310.1371/journal.pone.0009259https://doaj.org/article/c574ebcdbab043a18d593cd3ff463f922010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20174623/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Disturbances in the circadian pacemaker system are commonly found in individuals with depression and sleep-related problems. We hypothesized that some of the canonical circadian clock genes would be associated with depression accompanied by signs of disturbed sleep, early morning awakening, or daytime fatigue. We tested this hypothesis in a population-based sample of the Health 2000 dataset from Finland, including 384 depressed individuals and 1270 controls, all with detailed information on sleep and daytime vigilance, and analyzed this set of individuals with regard to 113 single-nucleotide polymorphisms of 18 genes of the circadian system. We found significant association between TIMELESS variants and depression with fatigue (D+FAT+) (rs7486220: pointwise P = 0.000099, OR = 1.66; corrected empirical P for the model of D+FAT+ = 0.0056; haplotype 'C-A-A-C' of rs2291739-rs2291738-rs7486220-rs1082214: P = 0.0000075, OR = 1.72) in females, and association to depression with early morning awakening (D+EMA+) (rs1082214: pointwise P = 0.0009, OR = 2.70; corrected empirical P = 0.0374 for the model D+EMA+; haplotype 'G-T' of rs7486220 and rs1082214: P = 0.0001, OR = 3.01) in males. There was significant interaction of gender and TIMELESS (for example with rs1082214, P = 0.000023 to D+EMA+ and P = 0.005 to D+FAT+). We obtained supported evidence for involvement of TIMELESS in sleeping problems in an independent set of control individuals with seasonal changes in mood, sleep duration, energy level and social activity in females (P = 0.036, = 0.123 for rs1082214) and with early morning awakening or fatigue in males (P = 0.038 and P = 0.0016, respectively, for rs1082214). There was also some evidence of interaction between TIMELESS and PER1 in females to D+FAT+ as well as between TIMELESS and ARNTL, RORA or NR1D1 in males to D+EMA+. These findings support a connection between circadian genes and gender-dependent depression and defective sleep regulation.Siddheshwar J UtgePia SoronenAnu LoukolaErkki KronholmHanna M OllilaSami PirkolaTarja Porkka-HeiskanenTimo PartonenTiina PaunioPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 2, p e9259 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Siddheshwar J Utge
Pia Soronen
Anu Loukola
Erkki Kronholm
Hanna M Ollila
Sami Pirkola
Tarja Porkka-Heiskanen
Timo Partonen
Tiina Paunio
Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.
description Disturbances in the circadian pacemaker system are commonly found in individuals with depression and sleep-related problems. We hypothesized that some of the canonical circadian clock genes would be associated with depression accompanied by signs of disturbed sleep, early morning awakening, or daytime fatigue. We tested this hypothesis in a population-based sample of the Health 2000 dataset from Finland, including 384 depressed individuals and 1270 controls, all with detailed information on sleep and daytime vigilance, and analyzed this set of individuals with regard to 113 single-nucleotide polymorphisms of 18 genes of the circadian system. We found significant association between TIMELESS variants and depression with fatigue (D+FAT+) (rs7486220: pointwise P = 0.000099, OR = 1.66; corrected empirical P for the model of D+FAT+ = 0.0056; haplotype 'C-A-A-C' of rs2291739-rs2291738-rs7486220-rs1082214: P = 0.0000075, OR = 1.72) in females, and association to depression with early morning awakening (D+EMA+) (rs1082214: pointwise P = 0.0009, OR = 2.70; corrected empirical P = 0.0374 for the model D+EMA+; haplotype 'G-T' of rs7486220 and rs1082214: P = 0.0001, OR = 3.01) in males. There was significant interaction of gender and TIMELESS (for example with rs1082214, P = 0.000023 to D+EMA+ and P = 0.005 to D+FAT+). We obtained supported evidence for involvement of TIMELESS in sleeping problems in an independent set of control individuals with seasonal changes in mood, sleep duration, energy level and social activity in females (P = 0.036, = 0.123 for rs1082214) and with early morning awakening or fatigue in males (P = 0.038 and P = 0.0016, respectively, for rs1082214). There was also some evidence of interaction between TIMELESS and PER1 in females to D+FAT+ as well as between TIMELESS and ARNTL, RORA or NR1D1 in males to D+EMA+. These findings support a connection between circadian genes and gender-dependent depression and defective sleep regulation.
format article
author Siddheshwar J Utge
Pia Soronen
Anu Loukola
Erkki Kronholm
Hanna M Ollila
Sami Pirkola
Tarja Porkka-Heiskanen
Timo Partonen
Tiina Paunio
author_facet Siddheshwar J Utge
Pia Soronen
Anu Loukola
Erkki Kronholm
Hanna M Ollila
Sami Pirkola
Tarja Porkka-Heiskanen
Timo Partonen
Tiina Paunio
author_sort Siddheshwar J Utge
title Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.
title_short Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.
title_full Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.
title_fullStr Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.
title_full_unstemmed Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.
title_sort systematic analysis of circadian genes in a population-based sample reveals association of timeless with depression and sleep disturbance.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/c574ebcdbab043a18d593cd3ff463f92
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