ABSTRACT
Genetic association study results serve three main purposes: (1) to identify risk markers that can be used to predict high-risk individuals who may benefit from earlier and more intensive interventions, as well as to define prognostic categories; (2) to gain insight into disease biology; and (3) to predict the response or degree of response to treatment (Figure 11.1). To date, the second aim has been the best fulfilled and the third aim has been of some clinical use. There has been no such success in translating the discovery of genetic markers to clinically useful markers for the prediction of future disease development and population screening. Given the number of statistically significant GWAS results, some with P values exceeding 10−250, it may sound paradoxical that we do not yet have predictive markers for disease development. This chapter discusses why there is, in fact, no paradox and also contrasts the current status of genetic risk profiling with the biological information obtained from genetic association studies. The development of biomarkers and assessment of their clinical utility is also covered. The emphasis is on GWASs, as they provide more complete coverage of the genome for identification of risk markers, but genetic risk profiling is also possible using the results of candidate gene studies. The latter approach would obviously generate a more limited risk profile.
