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Pharmacogenomic Applications in Children

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Pharmacogenomics and Personalized Medicine

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

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Abstract

Genetic diversity, together with specific environmental exposures, contributes to both disease susceptibility and interindividual variability in response to drugs. It has proven difficult to isolate disease genes that confer susceptibility to complex disorders, and as a consequence even fewer genetic variants that influence clinical response to drugs have been uncovered. As such, the candidate gene approach has largely failed to deliver and, although the family-based linkage approach has certain theoretical advantages in dealing with common/complex disorders, progress has been slower than was hoped. More recently, genome-wide association (GWA) studies have increasingly gained popularity and been found to be highly robust in identifying variants that associate with and predispose to complex disease, such as age-related macular degeneration, type 2 diabetes, and coronary artery disease. While these diseases dominantly affect adults, more recent studies have unveiled significant association of novel genes predisposing to Type 1 diabetes and autism, and replicated associations to IBD and obesity genes in children. In this regard, the Children's Hospital of Philadelphia recently founded a large-scale high-throughput genotyping program aimed at resolving the pathogenic mechanisms of complex pediatric disorders, through GWA studies of over 100,000 children. This has stirred new hope for the mapping of genes that regulate drug response related to pediatric conditions. Collectively, these studies support the notion that modern high-throughput SNP genotyping technologies, when applied to large and comprehensively phenotyped patient cohorts, capture the most clinically relevant disease-modifying and drug response genes. This review addresses both recent advances in the genotyping field, and some highlights from GWA studies, focusing on pediatric disorders, which have conclusively uncovered variants that underlie disease susceptibility and/or variability in drug response in common disorders.

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Authors and Affiliations

  1. The Center for Applied Genomics and Division of Human Genetics, the Abramson Research Center of the Joseph Stokes Jr. Research Institute, Department of Pediatrics, The Children's Hospital of Philadelphia of the University of Pennsylvania School of Medicine, Philadelphia, PA

    Struan F.A. Grant & Hakon Hakonarson

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  1. Struan F.A. Grant
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  1. Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Raritan, NJ, USA

    Nadine Cohen

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Grant, S.F., Hakonarson, H. (2008). Pharmacogenomic Applications in Children. In: Cohen, N. (eds) Pharmacogenomics and Personalized Medicine. Methods in Pharmacology and Toxicology. Humana Press. https://doi.org/10.1007/978-1-59745-439-1_20

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  • DOI: https://doi.org/10.1007/978-1-59745-439-1_20

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