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Background  Long-term sickness absences burden the economy in many industrialized countries. Both educational attainment and health behaviors are well-known predictors of sickness absence. It remains, however, unclear whether these associations are causal or due to confounding factors. The co-twin control method allows examining causal hypotheses by controlling for familial confounding (shared genes and environment). In this study, we applied this design to study the role of education and health behaviors in sickness absence, taking sex and cohort differences into account.    Methods  Participants were two cohorts of in total 8806 Norwegian twins born 1948 to 1960 (older cohort, mean age at questionnaire = 40.3, 55.8% women), and 1967 to 1979 (younger cohort, mean age at questionnaire = 25.6, 58.9% women). Both cohorts had reported their health behaviors (smoking, physical activity and body mass index (BMI)) through a questionnaire during the 1990s. Data on the twins’ educational attainment and long-term sickness absences between 2000 and 2014 were retrieved from Norwegian national registries. Random (individual-level) and fixed (within-twin pair) effects regression models were used to measure the associations between educational attainment, health behaviours and sickness absence and to test the effects of possible familial confounding.    Results  Low education and poor health behaviors were associated with a higher proportion of sickness absence at the individual level. There were stronger effects of health behaviors on sickness absence in women, and in the older cohort, whereas the effect of educational attainment was similar across sex and cohorts. After adjustment for unobserved familial factors (genetic and environmental factors shared by twin pairs), the associations were strongly attenuated and non-significant, with the exception of health behaviors and sickness absence among men in the older cohort.    Conclusions  The associations between educational attainment, health behaviors, and sickness absence seem to be confounded by unobserved familial factors shared by co-twins. However, the association between health behaviors and sickness absence was consistent with a causal effect among men in the older cohort. Future studies should consider familial confounding, as well as sex and age/cohort differences, when assessing associations between education, health behaviors and sickness absence.    Supplementary Information   Supplementary information  accompanies this paper at 10.1186/s12889-020-09741-y.

Education differences in sickness absence and the role of health behaviors: a prospective twin study