Paternal exposure to high levels of radioactivity causes heritable minisatellite mutations. However, the effect of more general paternal such as cigarette smoking, on germline mutations remains unexplored. We two of the most commonly used minisatellite loci (CEB1 and B6.7) to germline mutations in blood samples of complete mother-father-child the Norwegian Mother and Child Cohort Study (MoBa). The presence of subsequently related to general lifestyle factors, including paternal before the partner became pregnant. Paternally derived mutations at the locus (mutation frequency 0.07) were not affected by lifestyle. In gross yearly income as a general measure of a healthy lifestyle low-mutation frequencies at the CEB1 locus (P=0.047). Income was related to smoking behavior, and paternally derived CEB1 mutations were dependently increased when the father smoked in the 6 mo before vs. 0.05 in smoking and nonsmoking fathers, respectively (P=0.061). suggest that paternal lifestyle can affect the chance of heritable unstable repetitive DNA sequences. To our knowledge, this is the first reporting an effect of lifestyle on germline minisatellite mutation in a human population with moderate paternal exposures.-Linschooten, J. Verhofstad, N., Gutzkow, K., Olsen, A.-K., Yauk, C., Oligschlager, Y., G., van Schooten, F. J., Godschalk, R. W. L. Paternal lifestyle as a source of germline mutations transmitted to offspring.