Abstract
To find the correlations between genome-wide gene expression variations and sequence polymorphisms in inbred cross populations, we developed a statistical method to claim expression quantitative trait loci (eQTL) in a genome. The method is based on multiple interval mapping (MIM), a model selection procedure, and uses false discovery rate (FDR) to measure the statistical significance of the large number of eQTL. We compared our method with a similar procedure proposed by Storey et al. and found that our method can be more powerful. We identified the features in the two methods that resulted in different statistical powers for eQTL detection, and confirmed them by simulation. We organized our computational procedure in an R package which can estimate FDR for positive findings from similar model selection procedures. The R package, MIM-eQTL, can be found at http://www.statgen.ncsu.edu/~wzou/MIM.eQTL.html.
Similar content being viewed by others
References
Barton NH, Keightley PD et al (2002) Understanding quantitative genetic variation. Nat Rev Genet 3(1):11–21
Basten C, Weir B, Zeng Z et al (2002) QTL Cartographer, Version 1.17. Department of Statistics, North Carolina State University, Raleigh, NC
Benjamini Y, Yekutieli D (2001) The control of the false discovery rate in multiple testing under dependency. Ann Stat 29(4):1165–1188
Bing N, Hoeschele I (2005) Genetical genomics analysis of a yeast segregant population for transcription network inference. Genetics 105:041103 (page genetics)
Brem RB, Kruglyak L (2005) The landscape of genetic complexity across 5,700 gene expression traits in yeast. PNAS 102(5):1572–1577
Brem R, Yvert G, Clinton R, Kruglyak L et al (2002) Genetic dissection of transcriptional regulation in budding yeast. Science 296(5568):752–755
Bystrykh L, Weersing E, Dontje B, Sutton S, Pletcher MT, Wiltshire T, Su AI, Vellenga E, Wang J, Manly KF, Lu L, Chesler EJ, Alberts R, Jansen RC, Williams RW, Cooke MP, de Haan G et al (2005) Uncovering regulatory pathways that affect hematopoietic stem cell function using ‘genetical genomics’. Nat Genet 37(3):225–232
Chesler EJ, Lu L, Shou S, Qu Y, Gu J, Wang J, Hsu HC, Mountz JD, Baldwin NE, Langston MA, Threadgill DW, Manly KF, Williams RW et al (2005) Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function. Nat Genet 37(3):233–242
Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138(3):963–971
Doerge RW, Churchill GA (1996) Permutation tests for multiple loci affecting a quantitative character. Genetics 142(1):285–294
Efron B, Tibshirani R, Storey JD, Tusher V et al (2001) Empirical bayes analysis of a microarray experiment. J Am Stat Assoc 96(456):1151–1160
Ihmels J, Levy R, Barkai N et al (2004) Principles of transcriptional control in the metabolic network of Saccharomyces cerevisiae. Nat Biotechnol 22(1):86–92
Kao C-H, Zeng Z-B, Teasdale RD et al (1999) Multiple interval mapping for quantitative trait loci. Genetics 152(3):1203–1216
Lander E, Botstein D et al (1989) Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121(1):185–199
Marchini J, Donnelly P, Cardon LR et al (2005) Genome-wide strategies for detecting multiple loci that influence complex diseases. Nat Genet 37(4):413–417
Sax K (1923) The association of size differences with seed-coat pattern and pigmentation in Phaseolus vulgaris. Genetics 8(6):552–560
Schadt EE, Monks SA, Drake TA, Lusis AJ, Che N, Colinayo V, Ruff TG, Milligan SB, Lamb JR, Cavet G, Linsley PS, Mao M, Stoughton RB, Friend SH et al (2003). Genetics of gene expression surveyed in maize, mouse and man. Nature 422(6929):297–302
Storey JD, Tibshirani R (2003) Statistical significance for genomewide studies. Proc Natl Acad Sci U S A 100(16):9440–5
Storey JD, Akey JM, Kruglyak L et al (2005) Multiple locus linkage analysis of genomewide expression in yeast. PLoS Biol 3(8):e267
Valdar W, Solberg LC, Gauguier D, Burnett S, Klenerman P, Cookson WO, Taylor MS, Rawlins JN, Mott R, Flint J et al (2006) Genome-wide genetic association of complex traits in heterogeneous stock mice. Nat Genet 38(8):879–87
Wolfinger R, Gibson G, Wolfinger E, Bennett L, Hamadeh H, Bushel P, Afshari C, Paules R et al (2001) Assessing gene significance from cDNA microarray expression data via mixed models. J Comput Biol 8(6):625–637
Yvert G, Brem RB, Whittle J, Akey JM, Foss E, Smith EN, Mackelprang R, Kruglyak L et al (2003) Trans-acting regulatory variation in Saccharomyces cerevisiae and the rol e of transcription factors. Nat Genet 35(1):57–64
Zeng Z, Kao C, Basten C et al (1999) Estimating the genetic architecture of quantitative traits. Genet Res 74(3):279–289
Acknowledgement
The authors sincerely thank Dr. Leonid Kruglyak for the access of the wonderful yeast data set.
Funding
This work was partially supported by the USDA Cooperative State Research, Education and Extension Service, Grant Number 2005-00754.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zou, W., Zeng, ZB. Multiple interval mapping for gene expression QTL analysis. Genetica 137, 125–134 (2009). https://doi.org/10.1007/s10709-009-9365-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10709-009-9365-z