Sulkava, S;
Ollila, HM;
Alasaari, J;
Puttonen, S;
Harma, M;
Viitasalo, K;
Lahtinen, A;
... Paunio, T; + view all
(2017)
Common Genetic Variation Near Melatonin Receptor 1A Gene Linked to Job-Related Exhaustion in Shift Workers.
Sleep
, 40
(1)
, Article zsw011. 10.1093/sleep/zsw011.
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Abstract
STUDY OBJECTIVES: Tolerance to shift work varies; only some shift workers suffer from disturbed sleep, fatigue, and job-related exhaustion. Our aim was to explore molecular genetic risk factors for intolerance to shift work. METHODS: We assessed intolerance to shift work with job-related exhaustion symptoms in shift workers using the emotional exhaustion subscale of the Maslach Burnout Inventory-General Survey, and carried out a genome-wide association study (GWAS) using Illumina’s Human610-Quad BeadChip (n = 176). The most significant findings were further studied in three groups of Finnish shift workers (n = 577). We assessed methylation in blood cells with the Illumina HumanMethylation450K BeadChip, and examined gene expression levels in the publicly available eGWAS Mayo data. RESULTS: The second strongest signal identified in the GWAS (p = 2.3 × 10E-6) was replicated in two of the replication studies with p < .05 (p = 2.0 × 10E-4 when combining the replication studies) and indicated an association of job-related exhaustion in shift workers with rs12506228, located downstream of the melatonin receptor 1A gene (MTNR1A). The risk allele was also associated with reduced in silico gene expression levels of MTNR1A in brain tissue and suggestively associated with changes in DNA methylation in the 5' regulatory region of MTNR1A. CONCLUSIONS: These findings suggest that a variant near MTNR1A may be associated with job-related exhaustion in shift workers. The risk variant may exert its effect via epigenetic mechanisms, potentially leading to reduced melatonin signaling in the brain. These results could indicate a link between melatonin signaling, a key circadian regulatory mechanism, and tolerance to shift work.
| Type: | Article |
|---|---|
| Title: | Common Genetic Variation Near Melatonin Receptor 1A Gene Linked to Job-Related Exhaustion in Shift Workers |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/sleep/zsw011 |
| Publisher version: | http://doi.org/10.1093/sleep/zsw011 |
| Language: | English |
| Additional information: | © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society]. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences, Neurosciences & Neurology, genome-wide association study, job-related exhaustion, shift work, MTNR1A, DNA methylation, GENOME-WIDE ASSOCIATION, INDIVIDUAL-DIFFERENCES, INTERNAL DESYNCHRONIZATION, CIRCADIAN-RHYTHMS, NIGHT WORKERS, HUMAN BRAIN, METAANALYSIS, BURNOUT, SLEEP, METHYLATION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1524691 |
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