Assessment of global phase uncertainty in case-control studies

• Main Authors: van Houwelingen Hans C, Putter Hein, Houwing-Duistermaat Jeanine J, Uh Hae-Won
• Format: Article
• Language: English
• Published: BMC 2009-09-01
• Series: BMC Genetics
• Online Access: http://www.biomedcentral.com/1471-2156/10/54

<p>Abstract</p> <p>Background</p> <p>In haplotype-based candidate gene studies a problem is that the genotype data are unphased, which results in haplotype ambiguity. The <inline-formula><graphic file="1471-2156-10-54-i1.gif"/></inline-formula> measure <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> quantifies haplotype predictability from genotype data. It is computed for each individual haplotype, and for a measure of global relative efficiency a minimum <inline-formula><graphic file="1471-2156-10-54-i1.gif"/></inline-formula> value is suggested. Alternatively, we developed methods directly based on the information content of haplotype frequency estimates to obtain global relative efficiency measures: <inline-formula><graphic file="1471-2156-10-54-i2.gif"/></inline-formula> and <inline-formula><graphic file="1471-2156-10-54-i3.gif"/></inline-formula> 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.</p> <p>Results</p> <p>A new global relative efficiency measure <inline-formula><graphic file="1471-2156-10-54-i4.gif"/></inline-formula> 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 <inline-formula><graphic file="1471-2156-10-54-i4.gif"/></inline-formula> 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.</p> <p>Conclusion</p> <p>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.</p>