Genome-wide scan of job-related exhaustion with three replication studies implicate a susceptibility variant at the UST gene locus

Job-related exhaustion is the core dimension of burnout, a work-related stress syndrome that has several negative health consequences. In this study, we explored the molecular genetic background of job-related exhaustion. A genome-wide analysis of job-related exhaustion was performed in the GENMETS subcohort (n 1256) of the Finnish population-based Health 2000 study. Replication analyses included an analysis of the strongest associations in the rest of the Health 2000 sample (n 1660 workers) and in three independent populations (the FINRISK population cohort, n 10 753; two occupational cohorts, total n 1451). Job-related exhaustion was ascertained using a standard self-administered questionnaire (the Maslach Burnout Inventory (MBI)-GS exhaustion scale in the Health 2000 sample and the occupational cohorts) or a single question (FINRISK). A variant located in an intron of UST, uronyl-2-sulfotransferase (rs13219957), gave the strongest statistical evidence in the initial genome-wide study (P 1.55 10(7)), and was associated with job-related exhaustion in all the replication sets (P 0.05; P 6.75 10(7) from the meta-analysis). Consistent with studies of mood disorders, individual common genetic variants did not have any strong effect on job-related exhaustion. However, the nominally significant signals from the allelic variant of UST in four separate samples suggest that this variant might be a weak risk factor for job-related exhaustion. Together with the previously reported associations of other dermatan/chondroitin sulfate genes with mood disorders, these results indicate a potential molecular pathway for stress-related traits and mark a candidate region for further studies of job-related and general exhaustion.