Complex Disease

The process of target identification analyzes a complex disease process by dissecting it into its fundamental components. This makes it possible to identify the one that is most integral to the manifestation of the disease. Target identification aims to understand the biological processes related to a disease, and to identify its mechanism and the structure of individual elements of the disease. Commonly these individual elements are receptors, enzymes, etc., which become the target of new drugs. 

As pharmacogenetics and pharmacogenomics are not mutually exclusive, but even sometimes display overlapping features, both disciplines are aimed at better tailoring medical therapy for a given complex disease such as essential hypertension or other CVD. In the wake of new technologies to identify candidate region for whatever phenotype, more robust and complex bioinformatic analyses are necessary to... 

Colony-stimulating Factors Combinatorial Chemistry Compartment Competitive Antagonists Complement System Complement-type Repeat Complex Disease Compound Libraries Compound Optimization Computational Biology Computerized Tomography COMT... 

Carter MC, Uzzaman A, Scott LM, et al Pediatric mastocytosis routine anesthetic management for a complex disease. Anesth Analg 2008 107 422-427. Bonadonna R Zanotti R, Caruso B, et al Allergen-specific immunotherapy is safe and effective in patients with systemic mastocytosis and Hymenoptera allergy. J Allergy Clin Immunol 2008 121 256-257. 

Young SS, Ge N. Recursive partitioning analysis of complex disease pharmacogenetics studies. I. Motivation and overview. Pharmacogenomics 2005 6(1) 65-75. 

Zaykin DV, Young SS. Large recursive partitioning analysis of complex disease pharmacogenetic studies. II. Statistical considerations. Pharmacogenomics 2005 6(l) 77-89. 

Hypersensitivity to foreign epitopes Anti-idiotypic response to normal cells Immune complex disease Potential MPS toxicity D. Specific specificity... 

Swaroop, A, Branham, KEH, Chen, W, and Abecasis, G, 2007. Genetic susceptibility to age-related macular degeneration A paradigm for dissecting complex disease traits. Hum Mol Genet 16, R174—R182. 

Muller-Myhsok B, Abel L. Genetic analysis of complex diseases. Science 1997 275 1328-1330. 

Jorde LB. Linkage disequilibrium and the search for complex disease genes. Genome Res 2000 10 1435-1444. 

Growing experience with complex disease genetics has made clear the need to minimize type I error in genetic studies [41, 109]. Power is especially an issue for SNP-based association studies of susceptibility loci for phenomenon such as response to pharmacological therapy, which are extremely heterogeneous and which are likely to involve genes of small individual effect. Table 10.2 shows some simple estimation of required sample sizes of cases needed to detect a true odds ratio (OR) of 1.5 with 80% power and type I error probability (a) of either 0.05 or 0.005. 

Keavney B. Genetic association studies in complex diseases. J Hum Hypertens 58... 

Martin ER, Lai EH, Gilbert JR et al. SNPing away at complex diseases analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease. Am J Hum Genet 2000 67 383-394. 

Terwilliger JD, Weiss KM. Linkage disequilibrium mapping of complex disease fantasy or reality Curr Opin Biotechnol 1998 9 578-594. 

Weeks D, Lathrop G. Polygenic disease methods for mapping complex disease traits. Trends Genet 1995 11 513-519. 

Wright, AF, Carothers AD, Pirastu M. Population choice in mapping genes for complex diseases. Nature Genet 1999 23 397-404. 

As illustrated above, there appears to be multiple perspectives on the pharmacogenomics of PD since this complex disease seems to involve several pathogenic... 

This chapter reports the advances in our understanding of the pharmacogenetics of alcoholism and responses to alcohol and the search for genes that confer susceptibility to this common complex disease. 

Martin, E.R., et al., "SNPing Away at Complex Diseases Analysis of Single-Nucleotide Polymorphism around APOE in Alzheimer Disease," Am. J. Hum. Genet., 67, 383-394 (2000). 

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