Allele (and haplotype) frequencies typically differ among historically divergent populations. In pharmacogenetic studies, spurious associations may arise if the case (e.g., responder) and control (e.g., nonresponder) groups are drawn from genetically distinct subpopulations (e.g., based on race), even when matched for demographics or other characteristics. One approach to this problem is to test for association in cases and controls that are "genetically matched." Another is to use statistical methods based on allele frequencies at "reference" loci (e.g., in genes selected because they are unlikely to be related to drug response) to account for differences in genetic background. As pharmacogenetic data accumulate, there will be an increasing demand for population-specific data. However, there is a current need for the identification and use of reference populations, despite the inherent difficulties and ambiguities in defining such populations. In summary, the main point was that some form of defining reference population is better than none and better than each individual sponsor defining reference populations on a case-by-case basis.
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