A Platform for Large-scale Discovery in Common Disease: Project Summary A comprehensive understanding of the genome architecture variants underlying inherited human disease phenotypes and protective alleles will facilitate improved diagnosis, prognosis, disease management, and the development of new treatments for hundreds of millions of people worldwide. In support of this goal, we propose to apply our established, state-of-the-art DNA sequencing and analysis platform to comprehensively identify rare variation influencing susceptibility to common complex diseases corresponding to three disease themes: 1) cardiovascular disease and metabolic risk, 2) autoimmune disease including Type 1 diabetes and rheumatoid arthritis, and 3) developmental and degenerative diseases including cleft lip/palate, idiopathic scoliosis and macular degeneration. Where possible, we will leverage emerging methods and technology to advance the state of the field and achieve our program goals. Our approach extends the discovery power of low-cost whole genome sequencing (WGS) with innovative laboratory and computational techniques to comprehensively interrogate the full spectrum of human genome variation. We developed these studies with substantial input from expert collaborators whose continued involvement and disease-specific expertise will be critical for success. Ultimately, the diversity of our proposed projects - in ters of disease phenotypes, sample ancestries, and study designs - will provide a better understanding of the genetic architecture of common disease and the extent to which it is shared across world populations.

Public Health Relevance

A Platform for Large-scale Discovery in Common Disease: Project Narrative The Center will apply its established state-of-the-art DNA sequencing facility and genomic analysis expertise to discover the genes and sequence variants conferring risk and protection for multiple common, complex human diseases such as cardiovascular disease, stroke, rheumatoid arthritis, and age-related macular degeneration. The knowledge and resources generated by this program will be rapidly made available to the research community to empower their own studies. Understanding the relationship between genetics and common disease will lead to better prevention, diagnosis, and treatment, with the overall goal of improving human health.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
Application #
Study Section
Special Emphasis Panel (ZHG1)
Program Officer
Felsenfeld, Adam
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
Lin, Chien-Jung; Lin, Chieh-Yu; Stitziel, Nathan O (2018) Genetics of the extracellular matrix in aortic aneurysmal diseases. Matrix Biol 71-72:128-143
Regier, Allison A; Farjoun, Yossi; Larson, David E et al. (2018) Functional equivalence of genome sequencing analysis pipelines enables harmonized variant calling across human genetics projects. Nat Commun 9:4038
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
Stitziel, Nathan O; Khera, Amit V; Wang, Xiao et al. (2017) ANGPTL3 Deficiency and Protection Against Coronary Artery Disease. J Am Coll Cardiol 69:2054-2063
Stitziel, Nathan O (2017) Human genetic insights into lipoproteins and risk of cardiometabolic disease. Curr Opin Lipidol 28:113-119
Auer, Paul L; Stitziel, Nathan O (2017) Genetic association studies in cardiovascular diseases: Do we have enough power? Trends Cardiovasc Med 27:397-404
Ganel, Liron; Abel, Haley J; FinMetSeq Consortium et al. (2017) SVScore: an impact prediction tool for structural variation. Bioinformatics 33:1083-1085