Genome-wide approaches to identify pharmacogenetic contributions to adverse drug reactions.


Journal Article

Adverse drug reactions (ADRs) have a major impact on patients, physicians, health care providers, regulatory agencies and pharmaceutical companies. Identifying the genetic contributions to ADR risk may lead to a better understanding of the underlying mechanisms, identification of patients at risk and a decrease in the number of events. Technological advances have made the routine monitoring and investigation of the genetic basis of ADRs during clinical trials possible. We demonstrate through simulation that genome-wide genotyping, coupled with the use of clinically matched or population controls, can yield sufficient statistical power to permit the identification of strong genetic predictors of ADR risk in a prospective manner with modest numbers of ADR cases. The results of a 500,000 single nucleotide polymorphism analysis of abacavir-associated hypersensitivity reaction suggest that the known HLA-B gene region could be identified with as few as 15 cases and 200 population controls in a sequential analysis.

Full Text

Cited Authors

  • Nelson, MR; Bacanu, S-A; Mosteller, M; Li, L; Bowman, CE; Roses, AD; Lai, EH; Ehm, MG

Published Date

  • February 2009

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 23 - 33

PubMed ID

  • 18301416

Pubmed Central ID

  • 18301416

Electronic International Standard Serial Number (EISSN)

  • 1473-1150

International Standard Serial Number (ISSN)

  • 1470-269X

Digital Object Identifier (DOI)

  • 10.1038/tpj.2008.4


  • eng