About us

The GAC contributes to major genomic research initiatives, offering data analysis support, software and methods development, statistical consulting, study design, data coordination, and ongoing data quality assurance through the duration of a project. Research efforts are collaborative with University of Washington (UW) faculty and students who possess advanced expertise and a dedicated interest in biostatistics, statistical genetics, and public health genetics. Other collaborators come from other academic institutions, government, nonprofits, and the private sector.

Workshops

The GAC provides hands-on training to focused groups and the broad scientific community on topics related to quantitative genetics. Some of the workshops we have taught are:

• Computational Pipeline for WGS Data Module at the UW Summer Institute for Statistical Genetics (SISG) (2021; 2020; 2019; 2018)

Current

• Genomics Research to Elucidate the Genetics of Rare diseases (GREGoR) Consortium Data Coordinating Center
• Polygenic Risk Methods in Diverse Populations (PRIMED) Consortium Coordinating Center
• Population Genetic Issues for forensic DNA Profiles (NIJ)
• Development of scalable and user friendly engine to support genotype-phenotype association testing on BioData Catalyst powered by Seven Bridges
• Theoretical Population Genetics
• CODIS Support (FBI Project)
• Statistical Evaluation of Forensic Sequencing Profiles (NIJ)
• Predoctoral Training in Statistical Genetics (NIH Training Grant)

Past

• Trans-Omics for Precision Medicine (TOPMed) Data Coordinating Center
• Hispanic Community Health Study/Study Of Latinos (HCHS/SOL) Genetic Analysis Center
• Center for Inherited Disease Research (CIDR)
• Genomics and Randomized Trial Networks (GARNET) Coordinating Center
• Gene Environment Association Studies (GENEVA) Coordinating Center

Activities

• Data coordination
• Data cleaning (Quality Assurance/Quality Control) and harmonization
• Data analysis support and training
• Statistical software and methods development
• Consulting
• Research study design and planning
• Population and quantitative genetics methods and analysis
• Forensic genetics methods and analysis

Areas of Expertise

• Statistical genetics methods and analysis
• Quantitative genetics methods and analysis
• Population genetics methods and analysis
• Forensic genetics methods and analysis
• Ethical, Legal, and Social Implications (ELSI)
• Cloud computing

Overview

We develop open source software for analyzing genetic data.

UW GAC GitHub Repository

Central collection of publicly available source code across various GAC projects.

Docker images

Docker images containing GAC software.

R Packages

gdsfmt

The package gdsfmt provides a high-level R interface to CoreArray Genomic Data Structure (GDS) data files, which are portable across platforms and include hierarchical structure to store multiple scalable array-oriented data sets with metadata information.

Zheng, X., Levine, D., Shen, J. et al. A high-performance computing toolset for relatedness and principal component analysis of SNP data. Bioinformatics 28, 3326–3328 (2012). PMID: 23060615

GENESIS

An R package for single- and aggregate-variant genetic association testing using computationally efficient mixed models in samples with complex population and pedigree structure. Also provides tools for de-convoluting population and pedigree structure in genetic data.

Gogarten, S. M., Sofer, T., Chen, H. et al. Genetic association testing using the GENESIS R/Bioconductor package. Bioinformatics 35, 5346–5348 (2019). PMID: 31329242

GWASTools

Classes for storing very large GWAS data sets and annotation, and functions for GWAS data cleaning and analysis.

Gogarten, S. M., Bhangale, T., Conomos, M. P. et al. GWASTools: an R/Bioconductor package for quality control and analysis of genome-wide association studies. Bioinformatics 28, 3329–3331 (2012). PMID: 23052040

SeqArray

Big data management of whole-genome sequence variant calls with thousands of individuals: genotypic data (e.g., SNVs, indels and structural variation calls) and annotations in GDS files are stored in an array-oriented and compressed manner, with efficient data access using the R programming language.

Zheng, X., Gogarten, S. M., Lawrence, M. et al. SeqArray-a storage-efficient high-performance data format for WGS variant calls. Bioinformatics 33, 2251–2257 (2017). PMID: 28334390

SeqVarTools

An interface to the fast-access storage format for VCF data provided in SeqArray, with tools for common operations and analysis.

Gogarten SM, Zheng X, Stilp A (2021). SeqVarTools: Tools for variant data. R package version 1.30.0, https://github.com/smgogarten/SeqVarTools.

SNPRelate

A parallel computing toolset for relatedness and principal component analysis of SNP data.

Zheng, X., Levine, D., Shen, J. et al. A high-performance computing toolset for relatedness and principal component analysis of SNP data. Bioinformatics 28, 3326–3328 (2012). PMID: 23060615

TOPMed WGS analysis pipeline

Analysis pipeline for TOPMed whole genome sequencing project.

WGSAParsr

An R package the TOPMed DCC developed and uses to parse genetic variant annotation files produced by the WGSA annotation tool.

Tools on BioData Catalyst powered by Seven Bridges

Ancestry and Relatedness workflows

Workflows for genetic ancestry and relatedness inference, implementing methods including LD-pruning, PC-AiR, PC-Relate, KING-robust, and KING-ibdseg.

Annotation Explorer

Interactive application to explore, query, and study characteristics of an inventory of annotations for all possible SNVs, indels in dbSNP and variants called in TOPMed studies. This application can be used pre-GWAS to generate annotation-informed variant filters and groups for rare variant association testing, and post-GWAS for fine-mapping and variant prioritization.

Data Management tools

Tools to manipulate and format data files, such as, tool for merging multiple VCF/BCF files and filtering monomorphic variants, and tool for converting variant calls from VCF into GDS format.

GENESIS Association Testing workflows

Workflows for genetic association testing using the GENESIS R package. Available workflows include: fitting a null model, single variant association testing, aggregate variant association testing (including burden, SKAT, fastSKAT, and SMMAT methods), sliding window association testing, and tools for making Manhattan, QQ, and LocusZoom plots.

Quality Control tools

Workflows for variant and sample QC using WGS data. Available workflows include: Pedigree check, Heterozygosity by sample and XY chromosome depth.
 

Selected Publications

TOPMed

Stilp, A. M., Emery, L. S., Broome, J. G. et al. A System for Phenotype Harmonization in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Program. Am J Epidemiol 190, 1977–1992 (2021). PMID: 33861317. See associated harmonization documentation at https://github.com/UW-GAC/topmed-dcc-harmonized-phenotypes.

Hu, Y., Stilp, A. M., McHugh, C. P. et al. Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program. Am J Hum Genet 108, 874–893 (2021). PMID: 33887194

Taliun, D., Harris, D. N., Kessler, M. D. et al. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature 590, 290–299 (2021). PMID: 33568819

Statistical genetics and methods

Sofer, T., Zheng, X., Laurie, C. A. et al. Variant-specific inflation factors for assessing population stratification at the phenotypic variance level. Nat Commun 12, 3506 (2021). PMID: 34108454

Sofer, T., Zheng, X., Gogarten, S. M. et al. A fully adjusted two-stage procedure for rank-normalization in genetic association studies. Genet Epidemiol 43, 263–275 (2019). PMID: 30653739

Chen, H., Wang, C., Conomos, M. P. et al. Control for Population Structure and Relatedness for Binary Traits in Genetic Association Studies via Logistic Mixed Models. Am. J. Hum. Genet. 98, 653–666 (2016). PMID: 27018471

Conomos, M. P., Reiner, A. P., Weir, B. S. et al. Model-free Estimation of Recent Genetic Relatedness. Am. J. Hum. Genet. 98, 127–148 (2016). PMID: 26748516

Browning, B. L. & Browning, S. R. Genotype Imputation with Millions of Reference Samples. Am J Hum Genet 98, 116–126 (2016). PMID: 26748515

Buckleton, J., Curran, J., Goudet, J. et al. Population-specific FST values for forensic STR markers: A worldwide survey. Forensic Sci Int Genet 23, 91–100 (2016). PMID: 27082756

Graffelman, J. & Weir, B. S. Testing for Hardy-Weinberg equilibrium at biallelic genetic markers on the X chromosome. Heredity (Edinb) 116, 558–568 (2016). PMID: 27071844

Conomos, M. P., Miller, M. B. & Thornton, T. A. Robust inference of population structure for ancestry prediction and correction of stratification in the presence of relatedness. Genet. Epidemiol. 39, 276–293 (2015). PMID: 25810074

Browning, S. R. & Browning, B. L. Accurate Non-parametric Estimation of Recent Effective Population Size from Segments of Identity by Descent. Am J Hum Genet 97, 404–418 (2015). PMID: 26299365

Zheng, X. & Weir, B. S. Eigenanalysis of SNP data with an identity by descent interpretation. Theor Popul Biol 107, 65–76 (2016). PMID: 26482676

Zhu, Z., Bakshi, A., Vinkhuyzen, A. A. E. et al. Dominance genetic variation contributes little to the missing heritability for human complex traits. Am J Hum Genet 96, 377–385 (2015). PMID: 25683123

Nelson, S. C., Doheny, K. F., Pugh, E. W. et al. Imputation-based genomic coverage assessments of current human genotyping arrays. G3 (Bethesda) 3, 1795–1807 (2013). DOI: 10.1101/150219

HCHS/SOL

Conomos, M. P., Laurie, C. A., Stilp, A. M. et al. Genetic Diversity and Association Studies in US Hispanic/Latino Populations: Applications in the Hispanic Community Health Study/Study of Latinos. Am. J. Hum. Genet. 98, 165–184 (2016). PMID: 26748518

Browning, S. R., Grinde, K., Plantinga, A. et al. Local Ancestry Inference in a Large US-Based Hispanic/Latino Study: Hispanic Community Health Study/Study of Latinos (HCHS/SOL). G3 (Bethesda) 6, 1525–1534 (2016). PMID: 27172203

Nelson, S. C., Stilp, A. M., Papanicolaou, G. J. et al. Improved imputation accuracy in Hispanic/Latino populations with larger and more diverse reference panels: applications in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hum. Mol. Genet. 25, 3245–3254 (2016). PMID: 27346520

GENEVA

Laurie, C. C., Laurie, C. A., Smoley, S. A. et al. Acquired chromosomal anomalies in chronic lymphocytic leukemia patients compared with more than 50,000 quasi-normal participants. Cancer Genet 207, 19–30 (2014). PMID: 24613276

Laurie, C. C., Laurie, C. A., Rice, K. et al. Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nat Genet 44, 642–650 (2012). PMID: 22561516

Laurie, C. C., Doheny, K. F., Mirel, D. B. et al. Quality control and quality assurance in genotypic data for genome-wide association studies. Genet. Epidemiol. 34, 591–602 (2010). PMID: 20718045

See also Software for additional publications