The McDonnell Genome Institute at Washington University has received a $10 million grant from the National Heart, Lung and Blood Institute (NHLBI) for its part in a project that aims to uncover the genetics behind several lung diseases, including chronic obstructive pulmonary disease and interstitial pulmonary fibrosis, in a racially and ethnically diverse group of patients.
This study is part of the NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program, a nationwide initiative to analyze the complete DNA sequence (the whole genome) of patients taking part in large-scale clinical trials in the United States.
“Most other large genome sequencing projects have focused on Europeans and Caucasians,” Susan K. Dutcher, a professor of genetics, interim director of the McDonnell Genome Institute, and the project’s principal investigator, said in a university news release.
“With this program, we are including many people with other racial and ethnic backgrounds. Increasing the diversity of the groups being sequenced is important in understanding how genetic variations influence disease risk,” Dutcher added.
The Whole Genome Sequencing (WGS) project was the first step in broadening the understanding of human genetics. Now, the TOPMed program is adding new data, focusing on the analysis of the genetic basis of heart, lung, blood, and sleep disorders.
Several diseases have already known genetic variations to which they are linked, either as the disease’s underlying cause or as an active participant its progression. Recognizing the extent of genetic involvement in illnesses can improve understanding of their molecular mechanisms, and may lead to new ways of identifying those at risk of developing these diseases.
For this kind of analysis, researchers need a large sample size to evaluate DNA sequences in the context of disease progression and compare findings with those of healthy individuals. The program now has about 62,000 participants drawn from more than 30 clinical studies, such as NHLBI’s Women’s Health Initiative and the Framingham Heart Study.
But unlike the WGS project, which gathered genetic information mainly from whites of European descent, the TOPMed program intents to include ethnic groups underrepresented in research and more reflective of the U.S. population. At present, participants are of European descent (50%), African (30%), Hispanic or Latino descendent (10%), Asian (8%), and indigenous populations (2%), including Pacific Islanders.
“It’s also important that the total number of patients in the project is huge,” Dutcher said. “Early phases of TOPMed have already sequenced the genomes of 85,000 people. This year, for Washington University’s portion of the project, we’re sequencing the genomes of about 6,500 patients with lung diseases, primarily COPD [chronic obstructive pulmonary disease] and interstitial pulmonary fibrosis, a progressive scarring of lung tissue with variable causes, including autoimmunity.”
Other national genome sequencing centers in the program include the Broad Institute of MIT, Harvard University, Illumina, Macrogen Corporation, the New York Genome Center, and Northwest Genomics Center.
NHLBI is a part of the National Institutes of Health.