Abstract In this study we seek to understand how environmental factors influence the risk of developing schizophrenia (SZ) and bipolar disorder (BD) and how these risk factors interact with genetic risk for these disorders. SZ and BD are of major public health importance owing to their profound personal and societal costs. Major advances have been made in understanding the genetic architectures and specific loci conferring risk for these disorders individually and jointly. While robust, replicated findings for environmental risk factors for SZ have been identified, these have failed to materialize for BD. We intend to address to address this imbalance through parallel investigations of environmental risk for SZ and BD and explore possible interactions with genetic risk for these disorders. For this work, we will utilize data from the Swedish National Registers which contain data across the lifespan for the Swedish population (>10 million). Our first aim seeks to assess the impact of environmental risk factors on the development of SZ or BD and whether these are shared or divergent. These will include: urban living, infections, obstetric complications, migration, childhood adversity, cannabis use, and winter or spring birth. Additionally, an individual?s genes may differentially affect sensitivity to environmental exposures. Therefore, we will use both indirect (family history) and direct (molecular genetic) assessments of genetic risk for SZ and BD in relation to environmental exposures. Registry information available for this study is accurate and complete out to third degree relatives for total population measures of family history for these disorders (Aim 2). Existing molecular genetic data collected in Sweden for 10,059 SZ cases, 11,052 BD cases, and 22,138 controls will be used for analyses of directly measured genetic risk (Aim 3). Concurrent examination of BD and SZ will allow for direct comparisons of how environmental exposures act independently and in conjunction with genetic risk to shape these diagnoses. Elucidating the mechanisms which give rise to these related conditions may reveal opportunities for prevention efforts and therapeutic targets to ultimately reduce the personal and societal burdens of these devastating disorders.