Q&A: TOPMed early report on human genomic data

The assistive device was designed for procedures involving structures above patients’ shoulders.

Q. What is TOPMed and why is the paper published Feb. 10  in Nature important?

A. TOPMed is an abbreviation for the Trans-Omics for Precision Medicine program, one of the world’s largest genome sequencing projects to date.  This week it reports uncovering more than 400 million variants in the human genome sequence. The program brings together  nearly 1,000 researchers from leading scientific organizations, including Harvard University, Johns Hopkins University, the University of Michigan, and the University of Washington.

These researchers are seeking to increase the diversity of genetic studies and have compiled massive datasets. Their overall objective to advance precision medicine research among government agencies, research universities, and health care systems. Precision medicine is an approach to tailoring clinical treatments or therapies based on a genetic understanding of an individual’s underlying conditions.

The National Institutes of Health’s National Heart, Lung and Blood Institute sponsors the TOPMed program.  The research effort hopes to contributes to precision medicine by integrating studies of participants with longitudinal follow-up, with deep variant catalogs obtained from whole-genome sequencing and other genomic technologies.

The goals of the particular TOPMed study reported this week are: (1) to identify new insights into the genetic architecture of the heart, lung, and blood system as well as of sleep disorders; and (2) to improve the diagnosis, treatment and prevention of related conditions causing disability or death.  This will be done by making the data available to researchers everywhere.

The paper, “Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program,” published Feb. 10 online by the journal Nature, examines the genetic sequencing data of more than 53,000 individuals. It represents the first release of data.

TOPMed now has more than 130,000 participants. One of the most important aspects of the project is the diverse ethnic and racial representation of the study’s participants. People of Asian descent comprise 9%; Hispanic and Latino, 15%; African 47%; European 63%; and other groups at 4%.

Q. What are the paper’s most important findings?

A. The paper provides a roadmap to researchers worldwide on the resources available from the project. These can be leveraged to understand susceptibilities to common human diseases across diverse ancestries, and to establish a foundation for personalized disease prediction, prevention, diagnosis, and treatment.

It also points to a new catalogue of hundreds of millions of previously unknown sequence variants across the human genome.  This information is now available to all researchers. It also provides new insights into the types of variants, their frequency in human populations, their potential function, and the mutational processes that led to these variants. 

Q. Why should the public care about this paper?

A. Each year tens of millions of people die or are severely disabled from many of the diseases whose genetic linkages were studied. Those include: asthma, chronic obstructive pulmonary disease or COPD, hypertension, stroke, congenital heart disease, atrial fibrillation, congestive heart failure, hemophilia, sickle cell disease, and sleep disorders. By identifying associations among genomic data and other biological and clinical data available from TOPMed, researchers might be able to develop methods to help predict an individual’s risk for some of these common diseases, to determine how to modify outcomes, and to provide new avenues toward the treatment for and prevention.

Q. So, what happens next?

A. This paper represents the first release of data from the TOPMed study. This data can now be explored by scientists, researchers, clinicians, and others in their research in genomics and precision medicine. Moreover, the TOPMed work will continue and will deepen the types of genomic data available about the participants.

Q. What role did the University of Washington play in this study?

A. Nearly 40 scientists from the School of Public Health, the School of Medicine, and the Brotman Baty Institute for Precision Medicine participated in this study. For example, the Genetic Analysis Center in the Department of Biostatistics, part of the School of Public Health, hosts the national Data Coordinating Center for TOPMed.

Scientists at the UW Medicine’s Northwest Genomics Center in tthe Department of Genome Sciences and Brotman Baty Institute also participated. They collaborated with other leading genome centers across the country, including the New York Genome Center, Washington University Genome Center, the Baylor College of Medicine Genome Center, and the Broad Institute at Harvard and the Massachusetts Institute of Technology. They provided whole genome sequencing and will continue to bring genomic technologies to the project.

Together, the faculty and staff at the University of Washington will continue to work closely with others at the University of Michigan and other academic and research institutions associated with TOPMed to offer new resources to understand and improve treatments for some of the most common diseases in the United States. 

– Written by Dean Owen, Brotman Baty Institute

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