This project will develop a comprehensive array of new statistical methods for analyzing genome-wide association studies, and will apply these methods, and other appropriate methods, to perform in-depth analyses of NIH-funded association studies that attempt to unravel the genetic basis of common complex diseases. ? ? The overall objective is for the work to produce, and enable others to produce, discoveries and insights that aid the development of medical diagnostic tests, more effective therapies, and, ultimately, prevention of disease. Our focus will be primarily on developing new Bayesian statistical methods, which complement and improve on existing analysis approaches.
The specific aims i nclude the refinement of existing Bayesian statistical approaches to assessing correlation between genotype and quantitative phenotype to improve their robustness to deviations from underlying modeling assumptions; extension of these methods to allow analysis of binary (case/control) phenotypes, and family-based designs; and modification of these approaches to incorporate relevant biological prior information (e.g.~information on molecular pathways). The result will be a suite of tools, implemented in user-friendly software, for performing both single-marker and multi-marker analyses for many of the most commonly-used association study designs, including both quantitative and binary (case/control) phenotypes for population samples and parent-offspring trios. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
2R01HG002585-06
Application #
7373120
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Ramos, Erin
Project Start
2002-09-20
Project End
2011-07-31
Budget Start
2008-09-17
Budget End
2009-07-31
Support Year
6
Fiscal Year
2008
Total Cost
$497,500
Indirect Cost
Name
University of Chicago
Department
Genetics
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Zhu, Xiang; Stephens, Matthew (2018) Large-scale genome-wide enrichment analyses identify new trait-associated genes and pathways across 31 human phenotypes. Nat Commun 9:4361
Gerard, David; Stephens, Matthew (2018) Empirical Bayes shrinkage and false discovery rate estimation, allowing for unwanted variation. Biostatistics :
Al-Asadi, Hussein; Dey, Kushal K; Novembre, John et al. (2018) Inference and visualization of DNA damage patterns using a Grade of Membership Model. Bioinformatics :
Zhu, Xiang; Stephens, Matthew (2017) BAYESIAN LARGE-SCALE MULTIPLE REGRESSION WITH SUMMARY STATISTICS FROM GENOME-WIDE ASSOCIATION STUDIES. Ann Appl Stat 11:1561-1592
Dey, Kushal K; Hsiao, Chiaowen Joyce; Stephens, Matthew (2017) Visualizing the structure of RNA-seq expression data using grade of membership models. PLoS Genet 13:e1006599
Stephens, Matthew (2017) False discovery rates: a new deal. Biostatistics 18:275-294
Lu, Mengyin; Stephens, Matthew (2016) Variance adaptive shrinkage (vash): flexible empirical Bayes estimation of variances. Bioinformatics 32:3428-3434
Raj, Anil; Wang, Sidney H; Shim, Heejung et al. (2016) Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling. Elife 5:
Petkova, Desislava; Novembre, John; Stephens, Matthew (2016) Visualizing spatial population structure with estimated effective migration surfaces. Nat Genet 48:94-100
Shim, Heejung; Chasman, Daniel I; Smith, Joshua D et al. (2015) A multivariate genome-wide association analysis of 10 LDL subfractions, and their response to statin treatment, in 1868 Caucasians. PLoS One 10:e0120758

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