a statistical approach to finding overlooked genetic associations统计方法寻找忽视遗传关联.pdfVIP

Rider et al. BMC Bioinformatics 2010, 11:526 /1471-2105/11/526 METHODOLOGY ARTICLE Open Access A statistical approach to finding overlooked genetic associations Andrew K Rider1,3,4, Geoffrey Siwo2,3, Nitesh V Chawla1,4, Michael Ferdig2,3,4, Scott J Emrich1,3* Abstract Background: Complexity and noise in expression quantitative trait loci (eQTL) studies make it difficult to distinguish potential regulatory relationships among the many interactions. The predominant method of identifying eQTLs finds associations that are significant at a genome-wide level. The vast number of statistical tests carried out on these data make false negatives very likely. Corrections for multiple testing error render genome-wide eQTL techniques unable to detect modest regulatory effects. We propose an alternative method to identify eQTLs that builds on traditional approaches. In contrast to genome- wide techniques, our method determines the significance of an association between an expression trait and a locus with respect to the set of all associations to the expression trait. The use of this specific information facilitates identification of expression traits that have an expression profile that is characterized by a single exceptional asso- ciation to a locus. Our approach identifies expression traits that have exceptional associations regardless of the genome-wide signifi- cance of those associations. This property facilitates the identification of possible false negatives for genome-wide significance. Further, our approach has the property of prioritizing expression traits that are affected by few strong associations. Expression traits identified by this method may warrant additional study because their expression level may be affected by targeting genes near a single locus. Results: We demonstrate our method by identifying eQTL h