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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: Utge, Siddheshwar J., Soronen, Pia, Loukola, Anu, Kronholm, Erkki, Ollila, Hanna M., Pirkola, Sami, Porkka-Heiskanen, Tarja, Partonen, Timo, Paunio, Tiina
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823770/
https://www.ncbi.nlm.nih.gov/pubmed/20174623
http://dx.doi.org/10.1371/journal.pone.0009259
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author Utge, Siddheshwar J.
Soronen, Pia
Loukola, Anu
Kronholm, Erkki
Ollila, Hanna M.
Pirkola, Sami
Porkka-Heiskanen, Tarja
Partonen, Timo
Paunio, Tiina
author_facet Utge, Siddheshwar J.
Soronen, Pia
Loukola, Anu
Kronholm, Erkki
Ollila, Hanna M.
Pirkola, Sami
Porkka-Heiskanen, Tarja
Partonen, Timo
Paunio, Tiina
author_sort Utge, Siddheshwar J.
collection PubMed
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.
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spelling pubmed-28237702010-02-20 Systematic Analysis of Circadian Genes in a Population-Based Sample Reveals Association of TIMELESS with Depression and Sleep Disturbance Utge, Siddheshwar J. Soronen, Pia Loukola, Anu Kronholm, Erkki Ollila, Hanna M. Pirkola, Sami Porkka-Heiskanen, Tarja Partonen, Timo Paunio, Tiina PLoS One Research Article 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. Public Library of Science 2010-02-18 /pmc/articles/PMC2823770/ /pubmed/20174623 http://dx.doi.org/10.1371/journal.pone.0009259 Text en Utge et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Utge, Siddheshwar J.
Soronen, Pia
Loukola, Anu
Kronholm, Erkki
Ollila, Hanna M.
Pirkola, Sami
Porkka-Heiskanen, Tarja
Partonen, Timo
Paunio, Tiina
Systematic Analysis of Circadian Genes in a Population-Based Sample Reveals Association of TIMELESS with Depression and Sleep Disturbance
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823770/
https://www.ncbi.nlm.nih.gov/pubmed/20174623
http://dx.doi.org/10.1371/journal.pone.0009259
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