title: Genome-wide scan of job-related exhaustion with three replication studies implicate a susceptibility variant at the UST gene locus.
abstract: 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.
authors.affiliation: Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Sulkava
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Ollila
authors.forename: Kirsi
authors.initials: K
authors.lastname: Ahola
authors.forename: Timo
authors.initials: T
authors.lastname: Partonen
authors.forename: Katriina
authors.initials: K
authors.lastname: Viitasalo
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.forename: Maarit
authors.initials: M
authors.lastname: Lappalainen
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimäki
authors.forename: Jussi
authors.initials: J
authors.lastname: Vahtera
authors.forename: Jaana
authors.initials: J
authors.lastname: Lindström
authors.forename: Mikko
authors.initials: M
authors.lastname: Härmä
authors.forename: Sampsa
authors.initials: S
authors.lastname: Puttonen
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Tiina
authors.initials: T
authors.lastname: Paunio
mesh_terms: D000328:Adult; D002055:Burnout, Professional / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012307:Risk Factors; D015238:Sulfotransferases / Q000235:genetics*; D011795:Surveys and Questionnaires
chemical_list: D015238:Sulfotransferases; C118596:UST protein, human