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This chapter discusses the diagnosis and epidemiology of panic disorder (PD). Genetic studies, while instrumental, cannot alone address the etiological complexities of most psychiatric disorders. The chapter turns to two integrative approaches that combine genetics with other clinical or biological methods to target the underlying mechanisms. First, it discusses exploiting the relationship between psychiatric and non-psychiatric medical manifestations (the expanded spectrum approach). This approach is particularly relevant to PD, where the panic attacks are accompanied by a range of physiological responses that may be central to the etiology. Second, the chapter describes neurobiological phenotypes, and in particular, on using measures of brain structure and function to identify genetic variation, and studies the mechanisms via which genes can impact behavior. The chapter concludes with an overview of imaging genetic studies of PD, and particularly, of how data from imaging studies can be used to enhance the tractability of genetic targets.