Assessment of global phase uncertainty in case-control studies

BACKGROUND: In haplotype-based candidate gene studies a problem is that the genotype data are unphased, which results in haplotype ambiguity. The [Image: see text] measure [1] quantifies haplotype predictability from genotype data. It is computed for each individual haplotype, and for a measure of global relative efficiency a minimum [Image: see text] value is suggested. Alternatively, we developed methods directly based on the information content of haplotype frequency estimates to obtain global relative efficiency measures: [Image: see text] and [Image: see text] based on A- and D-optimality, respectively. All three methods are designed for single populations; they can be applied in cases only, controls only or the whole data. Therefore they are not necessarily optimal for haplotype testing in case-control studies. RESULTS: A new global relative efficiency measure [Image: see text] was derived to maximize power of a simple test statistic that compares haplotype frequencies in cases and controls. Application to real data showed that our proposed method [Image: see text] gave a clear and summarizing measure for the case-control study conducted. Additionally this measure might be used for selection of individuals, who have the highest potential for improving power by resolving phase ambiguity. CONCLUSION: Instead of using relative efficiency measure for cases only, controls only or their combined data, we link uncertainty measure to case-control studies directly. Hence, our global efficiency measure might be useful to assess whether data are informative or have enough power for estimation of a specific haplotype risk.