In this project we propose to develop statistical methods for the analysis of microarray and RNA-sequencing data for expression QTL mapping. Our project is designed to address a number of important methodological issues, with particular relevance to the forthcoming GTEx study. We propose to extend a Bayesian hierarchical model for cis-eQTL mapping to enable simultaneous mapping in multiple tissues, and to improve the use of external biological information. We also propose to develop methods to allow more sensitive detection of trans-acting eQTLs that are correlated with networks or modules of co-regulated genes. Finally, we aim to develop methods for estimating transcript abundances from RNA sequencing data, for use in QTL mapping.

Public Health Relevance

The purpose of this project is to develop new tools for analyzing and interpreting eQTL (expression quantitative trait loci) studies. We will develop analytical tools for both microarray-based and RNA-sequence-based measurements of gene expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
3R01MH090951-02S1
Application #
8509199
Study Section
Special Emphasis Panel (ZRG1-GGG-A (52))
Program Officer
Addington, Anjene M
Project Start
2010-09-17
Project End
2013-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$200,001
Indirect Cost
$68,349
Name
University of Chicago
Department
Genetics
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Chiang, Colby; Scott, Alexandra J; Davis, Joe R et al. (2017) The impact of structural variation on human gene expression. Nat Genet 49:692-699
Mohammadi, Pejman; Castel, Stephane E; Brown, Andrew A et al. (2017) Quantifying the regulatory effect size of cis-acting genetic variation using allelic fold change. Genome Res 27:1872-1884
Tan, Meng How; Li, Qin; Shanmugam, Raghuvaran et al. (2017) Dynamic landscape and regulation of RNA editing in mammals. Nature 550:249-254
Dolan, M Eileen; El Charif, Omar; Wheeler, Heather E et al. (2017) Clinical and Genome-Wide Analysis of Cisplatin-Induced Peripheral Neuropathy in Survivors of Adult-Onset Cancer. Clin Cancer Res 23:5757-5768
Yang, Fan; Wang, Jiebiao; GTEx Consortium et al. (2017) Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis. Genome Res 27:1859-1871
Agrawal, A; Chou, Y-L; Carey, C E et al. (2017) Genome-wide association study identifies a novel locus for cannabis dependence. Mol Psychiatry :
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Bai, Xue; Mangum, Kevin D; Dee, Rachel A et al. (2017) Blood pressure-associated polymorphism controls ARHGAP42 expression via serum response factor DNA binding. J Clin Invest 127:670-680
Mercader, Josep M; Liao, Rachel G; Bell, Avery D et al. (2017) A Loss-of-Function Splice Acceptor Variant in IGF2 Is Protective for Type 2 Diabetes. Diabetes 66:2903-2914
Peckham-Gregory, Erin C; Chakraborty, Rikhia; Scheurer, Michael E et al. (2017) A genome-wide association study of LCH identifies a variant in SMAD6 associated with susceptibility. Blood 130:2229-2232

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