The long-term objective of this research proposal is to provide the tools, analysis, and a framework to establish the connection between tissue-specific expression and heritable causes of complex disease, using data from the GTEx Project. The proposal is divided into four Aims: (i) To extend our development of linear eQTL models to the analysis of RNA-Seq exon-level and total read-count (TReC) mapping, and to include eQTL fingerprinting and quality-weighted regression;(ii) to develop new statistical methods for multi-tissue eQTL analysis;(iii) to identify allele-specific and isoform-specific eQTLs across multiple tissues, and (iv) to comprehensively evaluate GTEx relationships with disease by intersecting common and tissue-specific eQTL findings with disease-specific databases. This proposal will extend or develop several tools that will be key to the success of GTEx. Current versions of the tools are either slow or not designed for the multi-tissue setting. We will apply these tools to GTEx and work closely with other GTEx analysis groups, and the tools will have wide utility for the eQTL analysis community.

Public Health Relevance

The GTEx Project will examine patterns of gene expression across numerous tissues in a large number of human donors, and relate these patterns to the underlying DNA of these individuals. The results will be used to better determine how genes act to cause disease, by describing which underlying genetic variants cause variation in expression in the organs and tissues most relevant for various diseases. This application aims to provide the tools, analysis, and framework to identify which DNA variants affect the expression of genes in a manner that is common to many tissues, and which are specific to one or a few tissues. The results will be used to gain a better understanding of the complex patterns of DNA variation in causing complex disease.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-GGG-H (50))
Program Officer
Addington, Anjene M
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North Carolina State University Raleigh
Biostatistics & Other Math Sci
Schools of Arts and Sciences
United States
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Castel, Stephane E; Mohammadi, Pejman; Chung, Wendy K et al. (2016) Rare variant phasing and haplotypic expression from RNA sequencing with phASER. Nat Commun 7:12817
Long, Quan; Argmann, Carmen; Houten, Sander M et al. (2016) Inter-tissue coexpression network analysis reveals DPP4 as an important gene in heart to blood communication. Genome Med 8:15
Benitez-Buelga, Carlos; Vaclová, Tereza; Ferreira, Sofia et al. (2016) Molecular insights into the OGG1 gene, a cancer risk modifier in BRCA1 and BRCA2 mutations carriers. Oncotarget 7:25815-25
Hartmann, Katherine; Seweryn, Michał; Handleman, Samuel K et al. (2016) Non-linear interactions between candidate genes of myocardial infarction revealed in mRNA expression profiles. BMC Genomics 17:738
Hou, Liping; Bergen, Sarah E; Akula, Nirmala et al. (2016) Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder. Hum Mol Genet 25:3383-3394
Zhou, Yi-Hui; Wright, Fred A (2016) The projack: a resampling approach to correct for ranking bias in high-throughput studies. Biostatistics 17:54-64
Brinkmeyer-Langford, Candice L; Guan, Jinting; Ji, Guoli et al. (2016) Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains. Front Aging Neurosci 8:183
Gordon, Erin D; Palandra, Joe; Wesolowska-Andersen, Agata et al. (2016) IL1RL1 asthma risk variants regulate airway type 2 inflammation. JCI Insight 1:e87871
Zhou, Yi-Hui; Wright, Fred A (2015) Hypothesis testing at the extremes: fast and robust association for high-throughput data. Biostatistics 16:611-25
Pierson, Emma; GTEx Consortium; Koller, Daphne et al. (2015) Sharing and Specificity of Co-expression Networks across 35 Human Tissues. PLoS Comput Biol 11:e1004220

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