The rare-to-common disease journey: a winding road to new therapies

The study of genetic variants that cause rare diseases has been a central strategy of genetic research for the last century, but the contribution of rare variants to the multifactorial inheritance of common diseases has only recently emerged as an avenue to accelerate functional mapping of the human genome. This perspective defines rare and common diseases, surveys prospects for integrating their study to decipher pathogenic mechanisms, and cites current clinical hurdles of disease translation. We discuss the premise that research into rare disease etiology can inform our understanding of common illnesses and vice versa, identify impediments to progress in translating rare disease findings into common disease treatments, and offer suggestions for realizing the benefits of global health research in the discovery of rare disease variants.