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  1. Hundreds of genome-wide association studies have been performed in recent years to identify common variants that are associated with complex disease. Although there have been some notable success stories, overall common variation has explained little of the high heritability of these traits. It is likely that the use of whole-genome sequencing to extend the study of rare variation in complex diseases will greatly advance our understanding of perioperative biology.

  2. Preliminary candidate gene studies suggest that susceptibility to adverse perioperative events, including cardiac (myocardial infarction [MI], ventricular dysfunction, atrial fibrillation), neurologic, and renal, among others, is genetically determined.

  3. Potential applications of biomarkers in perioperative medicine and critical care include prognosis, diagnosis, and monitoring of adverse outcomes, as well as informing and refining therapeutic decisions. Very few so far have been rigorously evaluated to demonstrate additive performance to existing risk stratification models (clinical validity) or change therapy (clinical utility). Most promising among those are natriuretic peptides and C-reactive protein for cardiovascular risk prediction, and procalcitonin to assess infection in the critically ill.

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DNA technology has already changed our health care, the food we eat, and our criminal justice system. Underlying these profound societal implications is the process of elucidating the relationship between specific differences encoded in our DNA (ie, genotypes) and our interindividual variability in morphology, development, behavior, athletic prowess, physiology, and disease susceptibility (ie, phenotypes). Many common diseases like atherosclerosis, coronary artery disease, hypertension, diabetes, cancer, asthma, and our responses to stress, injury, drugs, and nonpharmacologic therapies are genetically complex, characteristically involving interplay of many genetic variations in molecular and biochemical pathways (ie, polygenic) and interactions between genes and environment (ie, multifactorial). In other words, complex phenotypes can be viewed as the integrated effect of many susceptibility genes and many environmental exposures. The proportion of phenotypic variance explained by genetic factors is referred to as heritability and can be estimated by examining the increased similarity of a phenotype in related as compared with unrelated individuals.

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In 2003 the 50th anniversary of Watson and Crick's description of the DNA double-helix structure also marked the completion of the Human Genome Project.1 This major accomplishment has provided the discipline of genomics with basic resources to study the functions of all genes in a systematic fashion, including their interaction with environmental factors, and to translate the findings into clinical and societal benefits. Functional genomics uses large-scale experimental methodologies and statistical analyses to investigate the regulation of gene expression in response to physiologic, pharmacologic, and pathologic changes. It also uses genetic information from clinical studies to examine the impact of genetic variability on disease characterization and outcomes. One of the major challenges and ongoing research efforts facing the postgenomic period is to connect the nearly 26,000 protein-coding genes of mammalian organisms to the genetic basis of complex polygenic diseases and the integrated function of complex biologic systems. The rapidly evolving field of genomic medicine proposes to use genomic information to assist medical ...

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