Purpose: To examine phenotypic considerations in the study of fatigue and to explore significant issues affecting the extension of biobehavioral research of fatigue by the inclusion of genetic and genomic markers. Theoretical Organization: Fatigue is a condition that has an adverse effect on quality of life that has been a focus of nursing inquiry. Yet, the study of fatigue has been stymied by the lack of phenotypic clarity. To expand the biobehavioral inquiry of fatigue, phenotypic clarity is needed. In addition, examining genomic factors associated with fatigue may help to elucidate the pathophysiology of fatigue and, in the future, lead to targeted interventions that address the molecular basis of fatigue. Conclusions: Given that nursing has been at the forefront of the study of fatigue, nurse scientists should consider enhancing phenotypic clarity by the development of a case-definition and use of a core measure of fatigue, one that can be augmented by condition- or population-specific measures as needed. Following the establishment of phenotypic clarity, the integration of genomics into biobehavioral research offers an opportunity for further clarity of phenotypes and for theoretical specification of the pathophysiology of conditions such as fatigue. Clinical Relevance: The development of targeted interventions for fatigue depend on a more precise definition of fatigue and a better understanding of the biologic processes that contribute to its development and persistence.
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