Discovery of genetic risk factors for disease

Advances in genomics have led to discovery of hundreds of mutations causing rare diseases and thousands of risk loci for complex diseases. As methods developed, I applied these first to map major genes in livestock and, more recently, to map genetic risk factors for common human diseases including melanoma and endometriosis. Genome-wide association studies (GWAS) have identified c. 10,000 genetic risk factors for human traits or diseases. These effects are small and a major challenge is that the results cannot be immediately translated into better understanding of disease biology or new drug targets. Major international efforts are in progress to bridge this gap and speed up target gene discovery with studies on genetic control of gene expression, epigenetic regulation and new high throughput methods to screen for functional consequences of GWAS ‘hits’. Understanding the genetic basis of disease is beginning to identify new drug targets, clarify the roles of environmental and biochemical exposures on disease development, and identify variants determining individual response to drugs. Translation and clinical applications will accelerate as the challenges to target gene identification are overcome