This project is an investigation of the gene by environment (GxE) interactions’ effect on substance use outcomes among refugee communities. Substance use disorders (SUDs) are a major public health concern, affecting individuals and communities worldwide. The etiology of SUDs is complex, involving a combination of genetic, environmental, and social factors. In recent years, there has been growing interest in the role of gene by environment interactions in the development of SUDs, particularly in vulnerable populations such as refugees. Refugee populations are exposed to a range of environmental stressors that may interact with genetic factors to increase their risk of SUDs. However, a number of studies describe a “refugee paradox,” where despite having been exposed to risk factors that can lead to SUDs, they are less likely to develop SUDs. Understanding these gene by environment interactions in refugee communities is crucial for not only understanding this phenomenon, but developing effective prevention and treatment strategies for this population. This thesis aims to investigate the gene by environment interactions underlying substance use in refugee communities and to analyze different methods for gene by environment analyses, ultimately determining which method is best suited for this population.