The Impact of Self-Reported Recurrent Headache on Absenteeism and Presenteeism at Work Among Finnish Municipal Female Employees

Purpose: The aim of this cross-sectional, observational study was to determine the impact of self-reported headache on absenteeism and presenteeism in a female working-age population.Subjects and Methods: The study population consisted of 594 Finnish female municipal employees, who answered self-administered questionnaires including sociodemographic, lifestyle, health, and work-related data. Sickness absence days were obtained from the official records of the employer. Headache recurrence was defined by asking whether headache was occasional or recurrent. Headache impact was measured by the HIT-6.Results: In our study, 456 (77%) females had headache, and headache was recurrent in 178 (39%). The self-reported recurrence of headache was related to age, AUDIT-C, health-rated quality-of-life, self-rated work ability, depressive symptoms, and work stress (P for linearity <0.001). They also had more depressive symptoms and work stress (P for linearity <0.001). Mental work load was highest in those with recurrent headache (P=0.042), and work engagement was highest in those without headache (P=0.038). There was no statistically significant difference in absenteeism days between the headache groups when adjusted with confounding variables. Presenteeism was associated with the recurrence of headache (P for linearity <0.001). Presenteeism and the HIT-6 score were significantly associated in the recurrent headache group (P=0.009).Conclusion: Headache was not related to absenteeism, but the self-reported recurrence of headache was clearly associated with presenteeism in this female working-age population

Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs

BackgroundNon-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines.ResultsWe confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual's methylation status is associated with the mother's age and socioeconomic status, but not with the individual's own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood.ConclusionsThese results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.</p

A genome-wide association study of CYP1A2 activity using tizanidine and caffeine as probe drugs

Cytochrome P450 (CYP) enzymes are the major drug metabolizing enzyme group. The highest level of CYPs is expressed in the liver, and the human cytochrome P450 (CYP) 1A2 is one of the major CYPs playing an important role in the metabolism of clinically used drugs. Muscle relaxant tizanidine and caffeine are sensitive substrates of CYP1A2. CYP1A2 enzyme activity is known to have interindividual variability. In this thesis a genome-wide association (GWA) study of the association of tizanidine and caffeine on CYP1A2 enzyme activity is performed. The pharmacokinetic data of this pooled analysis is based on 8 previously published studies assessing the co-effects and interactions of tizanidine with some other variable on CYP1A2 enzyme activity. Separate GWA studies were performed for men and women. Cigarette smoking was set as a covariate for men and the use of oral contraceptives was set as a covariate for women. These two GWA studies were combined into a genome-wide association meta-analysis and those results are analyzed in this thesis. Furthermore, replication of genome-wide significant findings in previous GWA studies on caffeine was sought. The variants tested in the genome-wide meta-analysis did not reach genome-wide significance (P < 5x10e-8). The replication study of the candidate SNVs in CYP1A2 and AHR loci showed clear signal, although they did not reach the genome-wide significance. This corroborates the previously published findings that CYP1A2 and AHR are the main genes involved in CYP1A2 enzyme activity. However, the results of the meta-analysis support the fact that the changes in CYP1A2 enzyme activity are a combination of various factors and can not be explained fully by genetics

Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs

Background: Non-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines. Results: We confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual’s methylation status is associated with the mother’s age and socioeconomic status, but not with the individual’s own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood. Conclusions: These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.publishedVersionPeer reviewe