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Nonclinical Statistics for Pharmaceutical and Biotechnology IndustriesGWAS for Drug Discovery

Nonclinical Statistics for Pharmaceutical and Biotechnology Industries: GWAS for Drug Discovery [Genome-wide association studies (GWAS) are playing a major role in identifying genetic associations with complex traits and disorders. It is anticipated this basic work will lead to a better understanding of the etiologies of such traits and disorders. In pharmacogenetics, application of GWAS methods is evolving. Here, the traits and disorders of interest derive from the diversity in patient response to medications. It is anticipated that GWAS will be successful in identifying the genotypes of individuals who respond well to a medication with correct dosages and highlighting those who will exhibit particular side effects. The GWAS process for a medication includes: (1) an appropriate study sample with variation in the medication response; (2) genotypes measured by arrays in members of the study sample; (3) quality control, imputation and correction for population stratification on the GWAS genotypes; (4) SNP association tested with the drug response using appropriate statistical methods for categorical and/or quantitative traits and appropriately corrected levels of statistical significance. In this chapter, GWAS is motivated by a brief summary of known pharmacogenetics findings. We then follow with the appropriate background information to understand the genetics concepts that support GWAS and a clear delineation of the statistical methods used to conduct and interpret a successful GWAS. We conclude with the future of this evolving methodology.] http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png

Nonclinical Statistics for Pharmaceutical and Biotechnology IndustriesGWAS for Drug Discovery

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Publisher
Springer International Publishing
Copyright
© Springer International Publishing Switzerland 2016
ISBN
978-3-319-23557-8
Pages
157 –176
DOI
10.1007/978-3-319-23558-5_7
Publisher site
See Chapter on Publisher Site

Abstract

[Genome-wide association studies (GWAS) are playing a major role in identifying genetic associations with complex traits and disorders. It is anticipated this basic work will lead to a better understanding of the etiologies of such traits and disorders. In pharmacogenetics, application of GWAS methods is evolving. Here, the traits and disorders of interest derive from the diversity in patient response to medications. It is anticipated that GWAS will be successful in identifying the genotypes of individuals who respond well to a medication with correct dosages and highlighting those who will exhibit particular side effects. The GWAS process for a medication includes: (1) an appropriate study sample with variation in the medication response; (2) genotypes measured by arrays in members of the study sample; (3) quality control, imputation and correction for population stratification on the GWAS genotypes; (4) SNP association tested with the drug response using appropriate statistical methods for categorical and/or quantitative traits and appropriately corrected levels of statistical significance. In this chapter, GWAS is motivated by a brief summary of known pharmacogenetics findings. We then follow with the appropriate background information to understand the genetics concepts that support GWAS and a clear delineation of the statistical methods used to conduct and interpret a successful GWAS. We conclude with the future of this evolving methodology.]

Published: Dec 29, 2015

Keywords: Pharmacogenetics; Gene mapping; SNPs; Association testing

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