Research Reveals More Than 275 Million Previously Unknown Genetic Variants

Researchers have identified more than 275 million previously unreported genetic variants via the All of Us Research Program, a longitudinal cohort study supported by the National Institutes of Health (NIH).^1,2

The discovery of the new variants was made possible by the fact that 46% of the 245,388 All of Us participants self-identified as having non-European ancestry, the researchers reported.¹ This is a major change from other large genomics studies, in which more than 90% of participants have European ancestry.²

The All of Us program is disease-agnostic, but researchers have already used the data to validate polygenic risk scores (PRSs) for 10 common health conditions, including breast cancer and prostate cancer.^3,4

“We determined that a PRS was validated if the odds ratios were statistically significant in a minimum of two and up to four ancestral populations: African/African American, Asian, European ancestry, and Hispanic/Latino,” the researchers noted.⁴ They explained that this approach was used to address health disparities caused by the clinical use of “Eurocentric” PRSs.

Researchers also analyzed data from more than 98,000 All of Us participants in an effort to determine differences in genetic variation among people with different ancestries.⁵ Rates of pathogenic variation ranged from 2.26% for participants of European ancestry to 1.32% for participants who identified as Latino/Admixed American, the researchers found. Pathogenic variants were most often observed in genes related to breast cancer and ovarian cancer or hypercholesterolemia.

“Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence,” the researchers explained. “This work will allow targeted precision medicine efforts at revealed disparities.”

Overall, the All of Us program has enrolled more than 750,000 people, and the NIH plans to enroll at least 1 million in total.²

“The All of Us dataset has already led researchers to findings that expand what we know about health — many that may not have been possible without our participants’ contributions of DNA and other health information,” Josh Denny, MD, chief executive officer of the All of Us Research Program, said in a statement.² “Their participation is setting a course for a future where scientific discovery is more inclusive, with broader benefits for all.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor