The study demonstrates how population-scale exome sequencing efforts, such as the Healthy Nevada Project, the largest health system-driven clinical exome sequencing initiative, improve our understanding of the human genome.
SAN MATEO, Calif. Jan. 29, 2020-- Researchers from Helix and Renown Health recently published the first-ever study to interrogate rare variants across two of the largest independent exome sequenced cohorts with thousands of clinical phenotypes.
Rare genetic variants often have larger effect sizes than common variants, and so are critical to enhancing our understanding of human health. But because they are difficult to find, they also are relatively understudied. Most research in human genetics to date has either been broad and large scale but limited to common and low frequency variants, or deep and narrow, focused on only a small number of phenotypes.
To address this gap, researchers at Helix and Renown Health analyzed rare variants (minor allele frequency < 0.1%) against more than 4,000 clinical phenotypes in approximately 70,000 exome-sequenced individuals from the UK Biobank and the Healthy Nevada Project. Researchers identified numerous statistically significant gene-based associations, including discovery and validation of a number of novel biomarkers across independent cohorts. The majority of these associations were driven by multiple rare variants per gene; 84% of the associations would not have been identified without the ability to deeply sequence each individual.
This study highlights the importance of using both deep and broad next-generation sequencing assays, such as Helix's proprietary Exome+™ assay. Because of the rarity of the variants analyzed and the need to look at multiple variants per gene, this study would not have been possible using technologies that rely heavily on statistical imputation such as microarrays or low coverage whole genome sequencing.
In addition, independent large-scale datasets comprising both high-quality exomes and clinical phenotypes have historically been very challenging to assemble, as the pace of studies was slow and the lack of diversity in many resources led to well-understood limitations. This data scarcity has limited the pace of research. The Healthy Nevada Project creates a real-world, diverse, and rapidly enrolling study that significantly advances population genomics.
"This is just the beginning of what we can uncover when we integrate large pools of deep genomic and clinical datasets," said Dr. James Lu, MD, PhD, co-founder and Chief Scientific Officer at Helix and one of the senior authors of the study. "We're excited to partner with Renown Health to show what's possible when you are able to scale health system genomic screening to the population-level."
"This research, and the data analytics platform behind it, allows Renown Health to investigate cancer, cardiac, respiratory illness and much more to identify underlying causes, assess real risks and eventually improve the health of our state by initiating appropriate preventive actions much earlier," said Anthony D. Slonim, MD, DrPH, President and CEO of Renown Health.
"This represents a new standard in human genetics research," said Dr. Joseph Grzymski, PhD, Chief Scientific Officer at Renown Health, Principal Investigator of the Healthy Nevada Project, and one of the senior authors of the study. "With the depth and scale of data we collect from the Healthy Nevada Project, we'll be able to shed new light on the influence of genetics on human health and change healthcare for the better."
The study titled "Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts" was led by scientists Elizabeth Cirulli, PhD and Nicole Washington, PhD of Helix and Dr. Joseph Grzymski, PhD of Renown Health and colleagues from Helix, Renown Health, and the Desert Research Institute. It can be accessed in Nature Communications.
Helix is the leading population genomics company working at the intersection of clinical care, research, and genomics. Its end-to-end platform enables health systems, life sciences companies, and payers to advance genomic research and accelerate the integration of genomic data into clinical care. Powered by one of the world's largest CLIA / CAP next-generation sequencing labs and its proprietary Exome+™ assay, Helix supports all aspects of population genomics including recruitment and engagement, clinically actionable disease screening, return of results, and basic and translational research. Learn more at www.helix.com.
About Renown Health
Renown Health is a locally governed and locally owned, not-for-profit integrated healthcare network serving Nevada, Lake Tahoe and northeast California. Renown is one of the region's largest private employers with a workforce of more than 7,000. It comprises three acute care hospitals, a rehabilitation hospital, the area's most comprehensive medical group and urgent care network, and the region's largest and only locally owned not-for-profit insurance company, Hometown Health. Renown Health's commitment has extended beyond traditional health care to include community health and well-being. Renown Health works to improve health care through science, research and genetics; forge community partnerships that improve lives and develop innovative models that are improving health care in Nevada. For more information, visit renown.org.