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Genetics and the general physician: insights, applications and future challenges Knight JCQJM 2009[Nov]; 102 (11): 757-72Scientific and technological advances in our understanding of the nature and consequences of human genetic variation are now allowing genetic determinants of susceptibility to common multifactorial diseases to be defined, as well as our individual response to therapy. I review how genome-wide association studies are robustly identifying new disease susceptibility loci, providing insights into disease pathogenesis and potential targets for drug therapy. Some of the remarkable advances being made using current genetic approaches in Crohn's disease, coronary artery disease and atrial fibrillation are described, together with examples from malaria, HIV/AIDS, asthma, prostate cancer and venous thrombosis which illustrate important principles underpinning this field of research. The limitations of current approaches are also noted, highlighting how much of the genetic risk remains unexplained and resolving specific functional variants difficult. There is a need to more clearly understand the significance of rare variants and structural genomic variation in common disease, as well as epigenetic mechanisms. Specific examples from pharmacogenomics are described including warfarin dosage and prediction of abacavir hypersensitivity that illustrate how in some cases such knowledge is already impacting on clinical practice, while in others prospective evaluation of clinical utility and cost-effectiveness is required to define opportunities for personalized medicine. There is also a need for a broader debate about the ethical implications of current advances in genetics for medicine and society.|Asthma/genetics[MESH]|Coronary Artery Disease/genetics[MESH]|Crohn Disease/genetics[MESH]|Female[MESH]|Genetic Predisposition to Disease/*genetics[MESH]|Genetic Variation[MESH]|Genome-Wide Association Study/*methods/trends[MESH]|HIV-1/genetics[MESH]|Humans[MESH]|Malaria/genetics[MESH]|Male[MESH]|Pharmacogenetics/*methods/trends[MESH]|Prostatic Neoplasms/genetics[MESH]|Venous Thrombosis/chemically induced/genetics[MESH] |