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The HapMap project and its application to genetic studies of drug response

The Pharmacogenomics Journal volume 4, pages 88–90 (2004)Cite this article

A central goal in the study of human biology is to understand the molecular basis of common disease, and variable sensitivity to drugs and other environmental factors. Adverse drug effects are a major cause of hospitalisation.1 The development of more effective, safer medicines requires understanding of the genetic factors which govern variable drug response in different individuals. Recent advances in genetics and genomics are paving the way to develop diagnostic tests that will enable the administration of drugs to be tailored to groups of individuals, and may in future help to define appropriate individual dosages and drug combinations in pharmacological treatment. These hopes are reflected in the growth of pharmacogenetic and pharmacogenomic research. Here we review the potential impact of current research in human genetic variation on our understanding and management of variable drug responses.

In the past 10 years, there has been great success in identifying the genetic basis of rare Mendelian disorders through linkage studies in large affected families. The genes and underlying mutations, which cause over 1400 such conditions, are reported in OMIM (http://www.ncbi.nlm.nih.gov). However, similar approaches have yielded much more modest success when applied to common, polygenic diseases and other phenotypes in which multiple genetic and environmental factors contribute to the risk that an individual has to develop disease. It is now widely accepted that association studies offer greater statistical power over linkage in detecting genetic effects underlying complex traits2 when the causative variant is common in the population. This power is determined by the allele frequency and risk ratio of the causative variant in relationship to the sample size. A key element in undertaking such studies is the establishment of a comprehensive catalogue of common variants in the human population.

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  1. Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK

    P Deloukas & D Bentley

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  1. P Deloukas
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  2. D Bentley
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Correspondence to P Deloukas.

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DUALITY OF INTEREST

The authors declare that they have no competing financial interests; both are members of the International HapMap consortium.

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Deloukas, P., Bentley, D. The HapMap project and its application to genetic studies of drug response. Pharmacogenomics J 4, 88–90 (2004). https://doi.org/10.1038/sj.tpj.6500226

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