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

The second strongest signal identified in the GWAS, observed at rs12506228, showed two independent replications and the meta-analysis for replication studies was highly significant ( p = 2.0 × 10E-4).

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In the meta- analysis of pilots, flight attendants, and nurses ( n = 59), three of these CpG sites presented nominally significant association ( p < .05) so that cg04188238 and cg12896146 showed higher methylation levels in association with the A allele of rs12506228 (cg04188238 β = 0.148, p = .0075, p Bonferroni = .114; cg12896146 β = 0.15, p = .019, p Bonferroni = .264) and cg10063179 lower methylation levels (β = −0.141, p = .0048, p Bonferroni = .074) ( Figure 4 , Supplementary Table S6).

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Post hoc analysis in this group showed a nonsignificant trend of association of rs12506228 with job-related exhaustion, but an opposite direction of effect, and a weaker size of effect, in comparison to other groups (β = −0.15, p = .08).

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