Statistical methods for expression quantitative trait loci (eQTL) mapping.
Traditional genetic mapping has largely focused on the identification of loci affecting one, or at most a few, complex traits. Microarrays allow for measurement of thousands of gene expression abundances, themselves complex traits, and a number of recent investigations have considered these measurements as phenotypes in mapping studies. Combining traditional quantitative trait loci (QTL) mapping methods with microarray data is a powerful approach with demonstrated utility in a number of recent biological investigations. These expression quantitative trait loci (eQTL) studies are similar to traditional QTL studies, as a main goal is to identify the genomic locations to which the expression traits are linked. However, eQTL studies probe thousands of expression transcripts; and as a result, standard multi-trait QTL mapping methods, designed to handle at most tens of traits, do not directly apply. One possible approach is to use single-trait QTL mapping methods to analyze each transcript separately. This leads to an increased number of false discoveries, as corrections for multiple tests across transcripts are not made. Similarly, the repeated application, at each marker, of methods for identifying differentially expressed transcripts suffers from multiple tests across markers. Here, we demonstrate the deficiencies of these approaches and propose a mixture over markers (MOM) model that shares information across both markers and transcripts. The utility of all methods is evaluated using simulated data as well as data from an F(2) mouse cross in a study of diabetes. Results from simulation studies indicate that the MOM model is best at controlling false discoveries, without sacrificing power. The MOM model is also the only one capable of finding two genome regions previously shown to be involved in diabetes.
Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin 53703, USA. kendzior@biostat.wisc.edu
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Kendziorski
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Chen
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Yuan
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Lan
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Attie
D000818:Animals; D002874:Chromosome Mapping / Q000706:statistics & numerical data; D003920:Diabetes Mellitus / Q000235:genetics; D005189:False Positive Reactions; D005819:Genetic Markers; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000032:analysis
D005819:Genetic Markers; D012333:RNA, Messenger