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genome-based clinical data. Cost One reason for slow adoption of pharmacogenetic testing is that data on cost-effectiveness are limited. This is obviously a complex issue that relates not only to the cost of genotyping itself but also to competing costs, such as those of caring for a patient with a catastrophic and predictable complication of drug therapy. Of note, however, a genotype needs to be established only once in a lifetime, and the costs of currently available tests are often less than those of the drugs themselves. Work toward overcoming the challenges described here has identified and highlighted specific obstacles in generating high-quality pharmacogenetic information and moving it from the research to the clinical setting and has, in some cases, pointed the way to solutions. Recognizing the challenges and the promise of pharmacogenetics, the National Institutes of Health initiated the Pharmacogenetics Research Network in 2000, with 3 overall goals: 1) to investigate the relationship of genetic variation to variable drug response; 2) to become an interactive network of investigators that impacts and elevates the field of pharmacogenetics with knowledge, tools, and resources; and 3) to create a publicly available knowledge base with reliable information that links phenotypes to genotypes. This knowledge base is available at www.pharmgkb.org and represents a central Web-enabled repository of variants in genes determining drug responses, their relationship to drug response phenotypes, and the strength of the evidence linking the two. This Web site is not only a repository but also a test bed that may enable advances in such areas as discovery of new associations or improved representations for drug response phenotypes. Although the concept of pharmacogenetics, 1 allele at a time, was first proposed over a century ago, the more recent term pharmacogenomics captures the essence of contemporary work in this field. In addition to studying single allelic variants with large clinical effects, investigators are beginning to explore much larger sets of genes, including pathways up to the whole genome, and how variations in these pathways may affect drug response. Pharmacogenomics is a young field that holds considerable promise of contributing to our understanding of the mechanisms underlying variability in human physiology and its response to drug therapy, with the potential to improve therapy. Indeed, studies in the field have discovered new biological mechanisms and have identified certain molecules, such as CYP2D6 or KCNH2, that are now routinely considered in drug development to enhance drug safety and are identifying new targets for drug action. Ultimately, identification of DNA variants before prescribing medication may become a routine feature of any patient–physician encounter. Although there are many challenges to be overcome in the implementation of pharmacogenetic vision in clinical practice, potential solutions are also evolving rapidly. Potential Financial Conflicts of Interest: Consultancies: D.M. Roden (GlaxoSmithKline, Pfizer Inc., AstraZeneca, Abbott Laboratories, Novartis, 1st Genetic Trust), R.M. Krauss (Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Merck & Co. Inc., Pfizer Inc., International Dairy Foods Association), M.J. Ratain (Prometheus, Genzyme Corp., Genentech), R.M. Weinshilboum (National Institutes of Health); S.T. Weiss (Glaxo-Wellcome, Roche Pharmaceuticals, Millennium Pharmaceuticals, Genetech, Schering-Plough, Variagenics, Genome Therapeutics, Merck Frost); Honoraria: D.M. Roden (GlaxoSmithKline, Pfizer, Inc., Astra-Zeneca, Abbott Laboratories, Novartis, 1st Genetic Trust), Dr. Krauss Neuropsychiatric symptoms (NPS) contribute substantially to the morbidity of Alzheimer disease (AD) and related disorders (ADRD). Psychotic symptoms of hallucinations and/or delusions frequently occur as the disease progresses and are among the most impairing NPS in AD(1). Regarding potential risk factors, vitamin D deficiency has been associated with both allcause dementia and AD(2, 3), and low levels of vitamin D are related to onset of psychotic symptoms in non-
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