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In this paper the development of statistical metamodels and statistical fast running models is presented first. They are utilized for propagating uncertainties in a multi-discipline design optimization process. Two main types of uncertainty can be considered in this manner: uncertainty due to variability in design variables or in random parameters; uncertainty due to the utilization of metamodels instead of the actual simulation models during the optimization process. The value of the new developments and their engagement in multi-discipline design optimization is demonstrated through a case study. An underwater vehicle is designed under four different disciplines, namely, noise radiation, self-noise due to TBL excitation, dynamic response due to propulsion impact loads, and response to an underwater detonation.