常见疾病相关常见遗传变异的临床应用

Twenty-five years after the draft of the human genome sequence, genomics has revolutionized many areas of biology, the diagnosis of familial and early-onset diseases, and the development of targeted therapies, particularly in oncology. Genomic knowledge has had little effect on the diagnosis and treatment of most common adult-onset conditions. Genomewide association studies have revealed that for these conditions, thousands of genetic variants of small effect underpin the polygenic nature of risk. When incorporated into polygenic risk scores, these variants predict risk; however, polygenic risk scores have had little effect in the clinic. In this article, we review the reasons for the slow pace of the diffusion of these methods in clinical practice. With the impending era of relatively inexpensive genome sequencing in mind, we review the ways in which polygenic risk scores, along with the related field of pharmacogenomics, may be useful in clinical practice for the prevention and treatment of common diseases.