From genetic variation to precision medicine.

ABSTRACT

Genetics has been an important tool for discovering new aspects of biology across life. In humans, there is growing momentum behind the application of this knowledge to drive innovation in clinical care, most notably through developments in precision medicine. Nowhere has the impact of genetics on clinical practice been more striking than in the field of rare disorders. For most of these conditions, individual disease susceptibility is influenced by DNA sequence variation in a single or a small number of genes. In contrast, most common disorders are multifactorial and are caused by a complex interplay of multiple genetic, environmental and stochastic factors. The longstanding division of human disease genetics into rare and common components has obscured the continuum of human traits and echoes aspects of the century-old debate between the Mendelian and biometric views of human genetics. In this article, we discuss the differences in data and concepts between rare and common disease genetics. Opportunities to unify these two areas are noted and the importance of adopting a holistic perspective that integrates diverse genetic and environmental factors is discussed.