As the United States marked its 250th anniversary, geneticists also had a reason to celebrate. The National Institutes of Health recently declared that the “All of Us” Research Program has become the largest global database combining health and genomic data. Initiated in 2015 during the Obama administration, the project aims to gather genetic and health information from a million Americans. Eleven years later, 747,000 participants have contributed their full genomes, lifelong health records, or both. Similar efforts are underway in the U.K., Canada, Germany, and Japan, but Alicia Martin from the Broad Institute hopes the U.S. database will be the most valuable due to the country’s diversity and healthcare system.
Martin, though not directly involved with “All of Us,” acknowledges the significant contributions of colleagues like Stacey Gabriel, Niall Lennon, and Heidi Rehm at the Broad Institute in generating the data, including extensive whole-genome sequencing. As a population and statistical geneticist, Martin is enthusiastic about using the “All of Us” database to understand the genetic and environmental factors affecting disease risk. She highlights the advanced stage reached since the Human Genome Project, noting the current database’s comprehensive nature with deeply sequenced genomes and longitudinal health records.
The inclusion of multi-omic data in the database is another significant feature. While DNA is fixed from birth, other components of the multi-ome, such as RNA and proteins, are dynamic and change throughout a person’s life. This comprehensive capture of biological activity provides deeper insights into health at any given time. Martin emphasizes that the “All of Us” database, with its focus on diverse U.S. populations, can identify novel biological insights not visible in more homogeneous populations.
Global biobanks like the U.K. Biobank are valuable for understanding disease biology. However, the U.S. initiative stands out for its diverse genetic representation, which has already led to breakthroughs such as the development of PCSK9 inhibitors. These discoveries, initially found in African American populations, highlight the importance of studying diverse groups. Martin points out that the database will benefit everyone, as discoveries made in subpopulations can inform treatment for broader groups.
Biobanks can enhance understanding of how genetics and life experiences combine to influence disease risk. The “All of Us” program allows researchers to study exposomics, which considers all life exposures that interact with genetics. This approach can quantify factors like smoking or pollution exposure and their impact on health. The database helps explore protective lifestyles that might counteract genetic predispositions and informs on disease progression and therapeutic responses.
With the rise of gene therapies, resources like “All of Us” gain new relevance. They help identify patients who would benefit from specific treatments, such as CRISPR gene-editing therapies. Martin cites examples like Victoria Gray, the first recipient of CRISPR therapy for sickle-cell disease, and Baby KJ, who received personalized CRISPR treatment. The database supports clinicians in targeting treatments to patients most likely to benefit, facilitating advancements in personalized medicine.
Original Source: news.harvard.edu
