Common Genetic Variation Near Melatonin Receptor 1A Gene Linked to Job-Related Exhaustion in Shift Workers

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 x 10E-6) was replicated in two of the replication studies with p 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.Peer reviewe

Environmental Stress Affects DNA Methylation of a CpG Rich Promoter Region of Serotonin Transporter Gene in a Nurse Cohort

Peer reviewe

Demographic data of the nurse groups by work stress.

<p>Demographic data of the nurse groups by work stress.</p

Representation of the <i>SLC6A4</i> gene promoter region for bisulfite sequencing analysis.

<p>Analyzed CpG sites are bolded and numbered from 1 through 5. Coordinates are based on the GRCh37 build (NCBI Reference Sequence: NC_000017.10).</p

Methylation in the promoter of <i>SLC6A4</i> at five CpG sites in high (grey) and low (white) work stress environments.

<p>Coordinates for each residue are 28 563 120 (CpG5), 28 563 109 (CpG4), 28 563 107 (CpG3), 28 563 102 (CpG2), and 28 563 090 (CpG1) as per GRCh37 build (NCBI Reference Sequence: NC_000017.10). Differences between work stress environments were significant as per t-test (p = 7.10E–06, p = 2.50E–05, p = 0.000292, p = 4.37E–06, and p = 0.000289 respectively). Standard errors are indicated.</p

Distribution of the 5-HTTLPR genotype.

<p>Distribution of the 5-HTTLPR genotype.</p