The importance of genetic factors in risk prediction has long been appreciated, and is exemplified in a simple form by the value of family history in predicting many complex diseases. Nevertheless, only a few specific molecular genetic variables have played an important role in historical risk predictions [e.g. BRCA1 and BRCA2 in familial breast and ovarian cancer (3)]. The success of recent genome-wide association studies (GWAS), however, has rapidly changed the outlook for genetic risk prediction. These studies have unlocked thousands of clearly validated genetic associations to complex diseases, but their generally weak effects have left their predictive value and clinical utility subject to hot debate.
