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Systemic sclerosis (SSc) is a chronic autoimmune disease of the connective tissues of unknown etiology, characterized mainly by fibrosis of the skin, vascular abnormalities, and systemic involvement of other organs, such as gastrointestinal tract, kidneys, lungs, and heart. SSc has been associated with a complex etiology with the involvement of both environmental and genetic factors in the onset and outcome of the disease. Although several major histocompatibility complex (MHC) and non‐MHC genes have been associated with the disease risk, there are several questions to answer. This article's purpose was to provide an extensive overview of the identified genetic factors in the etiopathogenesis of SSc.