Why do some seniors age in good health and other seniors suffer with multiple chronic conditions? A new genetic database is using whole-genomic sequencing (WGS) to answer that question in ways that may benefit medical laboratories.
Because of the rapid aging of populations in the United States and other developed nations throughout the world, there is keen interest in how to keep seniors healthy. In fact, developing effective lab testing services in support of improved senior health is one of the big opportunities for both clinical laboratories and anatomic pathology groups.
Until recent years, most clinical pathologists dealt primarily with lab tests that used specimens such as blood and urine. However, genetics researchers are using WGS to discover new causes for many chronic illnesses. And the tools these researchers are developing offer pathologists and clinical laboratories powerful new ways to help doctors diagnose disease.
One genetics study involved a collaboration between the Garvan Institute of Medical Research at the University of New South Wales (UNSW) and Monash University. The research, launched in 2012, resulted in a database called the Medical Genome Reference Bank (MGRB).
Through the use of WGS, the MGRB now features a huge database of thousands of healthy elderly people. The data it contains may enable pathology scientists to learn, from a genetic standpoint, why some people age healthfully while others do not.
The researchers published their work titled, “The Medical Genome Reference Bank: A Whole-Genome Data Resource of 4,000 Healthy Elderly Individuals. Rationale and Cohort Design,” in the European Journal of Human Genetics.
Finding New Applications for Genetic Data
According to the UNSW published study, “The MGRB is comprised of individuals consented through the biobank programs of two contributing studies … Each sample is from an individual who has lived to [greater than or equal to] 70 years with no reported history or current diagnosis of cardiovascular disease, dementia, or cancer, as confirmed by the participating studies at recent follow-up study visits.”
The researchers noted in their paper, “Aged and healthy populations are more likely to be selectively depleted of pathogenic alleles, and therefore particularly suitable as a reference population for the major diseases of clinical and public health importance.”
The MGRB plans to make its database openly accessible to the international research community through its website once all 4,000 samples have been sequenced. Currently, about 3,000 of the samples have been analyzed, as noted on the Garvan website, which is tracking the MGRB’s progress.
Personal Genetic Data in Precision Medicine
“The integration of genomic knowledge and technologies into healthcare is revolutionizing the way we approach clinical and public health practice,” Caron M. Molster, et al, noted in, “The Evolution of Public Health Genomics: Exploring Its Past, Present, and Future,” published in Frontiers in Public Health. Molster is Manager at the Health Department Western Australia in Perth, and lead author of the paper.
“Public health genomics has evolved to responsibly integrate advancements in genomics into the fields of personalized medicine and public health,” the researchers wrote.
The 100,000 Genomes Project in the United Kingdom is sequencing the genomes of people who have rare diseases and their families. Researchers all over the world are collecting genomic data with plans to use it in different ways, and on various chronic disease populations, in pursuit of precision medicine goals.
Molster and her co-authors noted the comparable development of genetic sequencing and precision medicine in their paper.
“Parallel to the developments in precision medicine has been the advancement of technologies that enable the production, aggregation, analysis, and dissemination of extremely large volumes of individual- and population-level data on genes, environment, behavior, and other social and economic determinants of health. These data have proven useful in finding new correlations, patterns and trends, particularly those involving complex interactions, in relation to diseases, pathogens, exposures, behaviors, susceptibility (risk), and health outcomes in populations,” they wrote.
According to Paul Lacaze, PhD, Head of the Public Health Genomics Program at Monash University, one of the challenges in interpreting whole-genome data in order to diagnose disease is “discriminating rare candidate disease-causing variants from the large numbers of benign variants unique to each individual. Reference populations are powerful filters,” he noted in the MGRB paper.
The MGRB database provides just such a powerful reference population, giving researchers who are studying specific diseases a tool for comparison.
Other Studies into Heathy Aging
Other initiatives to create datasets of genome information for specific populations also are underway. The Scripps Translational Science Institute (STSI) in La Jolla, Calif., has been studying healthy aging since 2007. That’s when STSI launched the Wellderly Study, according to a news release. As of 2016, they had sequenced the genomes of 600 study participants, as well as 511 samples for comparison from a study being conducted separately by the Inova Translational Medicine Institute, a paper in Nature noted.
Another effort being conducted in China involves a database called PGG.Population. These researchers seek to “create a comprehensive depository of geographic and ethnic variation of human genome, as well as a platform bringing influence on future practitioners of medicine and clinical investigators,” according to their 2018 paper published in Nucleic Acids Research.
In this case, rather than identifying common genomic variants among a specific population, such as the healthy elderly, the researchers are working to understand how genetic variations are distributed among specific populations. “The PGG.Population database documents 7,122 genomes representing 356 global populations from 107 countries and provides essential information for researchers to understand human genomic diversity and genetic ancestry,” wrote the researchers.
Each of these disparate datasets represents paths of investigation that could lead to a better understanding of personal and public health. As technologies continue to develop that enable scientists to sift through the massive amount of WGS data being generated, a clearer picture of what healthy aging at the genetic level looks like will likely emerge.
Precision medicine is leading to precision public health, and clinical pathology laboratories are important parts of the public health puzzle.