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Clinical Laboratories and Pathology Groups

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Orchid Health Announces Release of First Commercially-Available Whole Genome Sequencing Service for Certain Diseases in Preimplantation Embryos

Clinical laboratory managers should note that this company’s new diagnostic offering involving screening embryos for specific genetic conditions is not without controversy

Is the world ready for whole genome sequencing (WGS) of preimplantation embryos to help couples undergoing in vitro fertilization (IVF) treatments know if their embryos  have potential genetic health problems? Orchid Health, a clinical preimplantation genetic testing (PGT) laboratory that conducts genetic screening in San Francisco, believes the answer is yes! But the cost is high, and the process is not without controversy.

According to an article in Science, Orchid’s service—a sequencings of the whole human genome of preimplantation embryos at $2,500 per embryo tested—“will look not just for single-gene mutations that cause disorders such as cystic fibrosis, but also more extensively for medleys of common and rare gene variants known to predispose people to neurodevelopmental disorders, severe obesity, and certain psychiatric conditions such as schizophrenia.”

However, Science also noted that some genomics researchers “claim the company inappropriately uses their data to generate some of its risk estimates,” adding that the “Psychiatric Genomics Consortium (PGC), an international group of more than 800 researchers working to decode the genetic and molecular underpinnings of mental health conditions, says Orchid’s new test relies on data [PGC] produced over the past decade, and that the company has violated restrictions against the data’s use for embryo screening.”

There are some who assert that a whole genome sequence of an embryo—given today’s state of genetic technology and knowledge—could generate information that cannot be interpreted accurately in ways that help parents and doctors make informed prenatal testing decisions. At the same time, criticisms expressed by the PGC raise reasonable points.

Perhaps this is a sign of the times. Orchid Health is the latest genetic testing company that is looking to get ahead of genetic testing competitors with its diagnostics offerings. Meanwhile, knowledgeable and credible experts question the appropriateness of this testing, given the genetic knowledge that exists today.

Noor Siddiqui

“This is a major advance in the amount of information parents can have,” Orchid’s founder and CEO Noor Siddiqui (above) told CNBC. “The way that you can use that information is really up to you, but it gives a lot more control and confidence into a process that, for all of history, has just been totally left to chance.” Should Orchid Health’s analysis prove useful, pediatricians could order further clinical laboratory prenatal testing to confirm and diagnose potential genetic diseases for parents. (Photo copyright: General Assembly.)

Orchid Receives World-class Support

Regardless of the pushback from some genetic researchers, Orchid has attracted several world-class geneticists and genetics investors to its board of advisors. They include:

The WGS test, according to Orchid, detects genetic errors in embryos that are linked to severe illnesses before a pregnancy even begins. And by sequencing 99% of an embryo’s DNA, the test can spot potential health risks that could affect a future baby.

According to its website, the PGT lab company uses the WGS data to identify both monogenic (single-gene) and polygenic (multiple-gene) diseases, including:

The company also claims its genetic screening can predict the risk of brain health issues in the unborn, such as Alzheimer’s disease, bipolar disorder, and schizophrenia, as well as heart health issues such atrial fibrillation and coronary artery disease.

Other health problems such as celiac disease and Type I/II diabetes also can be forecasted with the test, Orchid claims. 

Not all Genetics Experts Agree

Orchid is not without its critics. Knowledgeable, credible experts have questioned the appropriateness of this type of genetic testing. They fear it could become a modern-day form of eugenics.

Andrew McQuillin, PhD, Professor of Molecular Psychiatry at University College London, has concerns about Orchid’s preimplantation genetic testing. He maintains that it is difficult to control how such data is used, and that even the most accurate sequencing techniques do not predict disease risk very well. 

“[Polygenic risk scores are] useful in the research context, but at the individual level, they’re not actually terribly useful to predict who’s going to develop schizophrenia or not,” McQuillin told Science. “We can come up with guidance on how these things should be used. The difficulty is that official guidance like that doesn’t feature anywhere in the marketing from these companies.”

McQuillin also stated that researchers must have an extensive discussion regarding the implications of this type of embryo screening.

“We need to take a look at whether this is really something we should be doing. It’s the type of thing that, if it becomes widespread, in 40 years’ time, we will ask, ‘What on Earth have we done?’” McQuillin emphasized.

Redefining Reproduction

It takes about three weeks for couples to receive their report back from Orchid after completing the whole genome sequence of a preimplantation embryo. A board-certified genetic counselor then consults with the parents to help them understand the results. 

Founder and CEO Noor Siddiqui hopes Orchid will be able to scale up its operations and introduce more automation to the testing process to the cost per embryo.

“We want to make this something that’s accessible to everyone,” she told CNBC.

“I think this has the potential to totally redefine reproduction,” she added. “I just think that’s really exciting to be able to make people more confident about one of the most important decisions of their life, and to give them a little bit more control.”

Clinical laboratories have long been involved in prenatal screening to gain insight into risk levels associated with certain genetic disorders. Even some of that testing comes with controversy and ambiguous findings. Whether Orchid Health’s PGT process delivers accurate, reliable diagnostic insights regarding preimplantation embryos remains to be seen.

—JP Schlingman

Related Information:

Genetics Group Slams Company for Using Its Data to Screen Embryos’ Genomes

Reproductive Startup Launches Test to Identify an Embryo’s Genetic Defects Before an IVF Pregnancy Begins

What Is the Difference Between Monogenic and Polygenic Diseases?

First Clinical Validation of Whole Genome Screening on Standard Trophectoderm Biopsies of Preimplantation Embryos

Orchid Tests Embryos for Genetic Diseases. It Just Raised $12 Million with This 11-Slide Pitch Deck

University of Washington Researchers Use Genomic Analysis to Track Shigella Infections as Decreased Cost of Gene Sequencing Aids Public Health Research

Another study in the United Kingdom that also used genomic analysis to understand drug-resistant Shigella produced findings that may be useful for microbiologists and medical laboratory scientists

From the onset of an infectious disease outbreak, public health officials, microbiologists, and clinical laboratory managers find it valuable to trace the origin of the spread back to the “index case” or “patient zero”—the first documented patient in the disease epidemic. Given the decreased cost of genomic analysis and improved accuracy of gene sequencing, infectious disease researchers are finding that task easier and faster than ever.

One recent example is a genomic study conducted at University of Washington (UW) in Seattle that enabled researchers to “retrace” the origin and spread of a “multidrug-resistant Shigellosis outbreak” from 2017 to 2022. “The aim of the study was to better understand the community transmission of Shigella and spread of antimicrobial resistance in our population, and to treat these multi-drug resistant infections more effectively,” the UW scientists stated in a new release.

Shigellosis (aka, bacillary dysentery) is a highly contagious disease of the intestines that can lead to hospitalization. Symptoms include fever, stomach cramps, diarrhea, dysentery, and dehydration.

“Additional analysis of the gut pathogen and its transmission patterns helped direct approaches to testing, treatment, and public health responses,” the UW news release states.

Usually prevalent in countries with public health and sanitation limitations, the “opportunistic” Shigella pathogen is now being seen in high-income countries as well, UW reported.

The researchers published their findings in Lancet Infectious Diseases, titled, “Genomic Reconstruction and Directed Interventions in a Multidrug-Resistant Shigellosis Outbreak in Seattle, WA, USA: A Genomic Surveillance Study.”

Ferric Fang, MD

“You can’t really expect an infectious disease to remain confined to a specific at-risk population. [Shigella infections are] very much an emerging threat and something where our public health tools and therapeutic tools have significant limitations,” infectious disease specialist Ferric Fang, MD (above) told CIDRAP News. Fang is a UW professor of Microbiology and Clinical Laboratory Medicine and a corresponding author of the UW study. (Photo copyright: University of Washington.)

Why are Shigella Cases Increasing?

The US Centers for Disease Control and Prevention (CDC) records more than 450,000 shigellosis infections each year in the US. The most common species in the US, according to CDC statistics, is Shigellaa sonnei.

Other members of the genus include:

Generally, Shigella infects children, travelers, and men who have sex with men (MSM), the CDC noted.

The UW researchers were motivated to study Shigella when they noticed an uptick in drug-resistant shigellosis cases in Seattle’s homeless population in 2020 at the beginning of the COVID-19 pandemic, Center for Infectious Disease Research and Policy News (CIDRAP News) reported.

“Especially during the pandemic, a lot of public facilities were closed that homeless people were used to using,” infectious disease specialist Ferric Fang, MD, told CIDRAP News. Fang is Professor of Microbiology and Laboratory Medicine at University of Washington and corresponding author of the UW study.

The researchers studied 171 cases of Shigella identified from 2017 to 2022 by clinical laboratories at Harborview Medical Center and UW Medical Center in Seattle. According to CIDRAP News, the UW researchers found that:

  • 46% were men who have sex with men (MSM).
  • 51% were people experiencing homelessness (PEH).
  • Fifty-six patients were admitted to the hospital, with eight to an intensive care unit.
  • 51% of isolates were multi-drug resistant (MDR).

Whole-Genome Sequencing Reveals Origin

The UW scientists characterized the stool samples of Shigella isolates by species identification, phenotypic susceptibility testing, and whole-genome sequencing, according to their Lancet Infectious Diseases paper. The paper also noted that 143 patients received antimicrobial therapy, and 70% of them benefited from the treatment for the Shigella infection.

Whole-genome sequencing revealed that two strains of Shigella (S. flexneri and S. sonnei) appeared first in Seattle’s MSM population before infecting the PEM population.

The genomic analysis found the outbreak of drug-resistant Shigella had international links as well, according to CIDRAP News:

  • One S. flexneri isolate was associated with a multi-drug resistant (MDR) strain from China, and
  • S. sonnei isolates resembled a strain characteristic of a current outbreak of MDR Shigella in England.

“The most prevalent lineage in Seattle was probably introduced to Washington State via international travel, with subsequent domestic transmission between at-risk groups,” the researchers wrote.

“Genomic analysis elucidated not only outbreak origin, but directed optimal approaches to testing, treatment, and public health response. Rapid diagnostics combined with detailed knowledge of local epidemiology can enable high rates of appropriate empirical therapy even in multidrug-resistant infection,” they continued.

UK Shigella Study Also Uses Genomics

Another study based in the United Kingdom (UK) used genomic analysis to investigate a Shigella outbreak as well.

Motivated by a UK Health Security Agency report of an increase in drug-resistance to common strains since 2021, the UK researchers studied Shigella cases from September 2015 to June 2022.

According to a paper they published in Lancet Infectious Diseases, the UK researchers “reported an increase in cases of sexually transmitted S. flexneri harboring blaCTX-M-27 (an antibiotic-resistant gene) in England, which is known to confer resistance to third-generation cephalosporins (antibiotics),” the researchers wrote.

Their analysis of plasmids (DNA with genes having antibiotic resistance) revealed a link in two drug-resistant Shigella strains at the same time, CIDRAP News explained.

“Our study reveals a worsening outlook regarding antimicrobial-resistant Shigella strains among MSM and highlights the value of continued integration of genomic analysis into surveillance and research,” the UK-based scientists wrote.

Current challenges associated with Shigella, especially as it evades treatment, may continue to demand attention from microbiologists, clinical laboratory scientists, and infectious disease specialists. Fortunately, use of genomic analysis—due to its ongoing improvements that have lowered cost and improved accuracy—has made it possible for public health researchers to better track the origins of disease outbreak and spread.    

Donna Marie Pocius

Related Information:

Genomic Reconstruction and Directed Interventions in a Multidrug-Resistant Shigellosis Outbreak in Seattle, Washington, USA: a Genomic Surveillance Study.

Genomics Aids Study of Seattle 2017-22 Shigella Outbreak

Q/A: Shigella—Shigellosis

A Spotlight on Growing Threat of Drug-Resistant Shigella

Emergence of Extensively Drug-Resistant and Multidrug-Resistant Shigella flexneri serotype 2a Associated with Sexual Transmission Among Gay, Bisexual, and Other Men Who Have Sex with Men, in England: A Descriptive Epidemiological Study

Two New York City Hospitals Join New Genetic Study to Perform Whole Genome Sequencing on 100,000 Newborn Babies to Search for 250 Rare Diseases

Goal is to demonstrate how whole human genome sequencing of newborns can deliver important diagnostic findings associated with 250 genetic conditions

Clinical laboratory testing and genetics are moving closer to the delivery room than ever before. In the largest study of its kind in North America, genomic scientists plan to supplement traditional screening for inherited diseases—traditionally performed on a blood sample taken shortly after birth—with whole genome sequencing (WGS) on 100,000 newborns in New York City during their first five years of life, LifeSciencesIntelligence reported.

Conducted by genetic scientists at NewYork-Presbyterian (NYP) and Columbia University, in collaboration with genetic company GeneDx, a wholly-owned subsidiary of health intelligence company Sema4 (NASDAQ:SMFR), the genetic research study, called GUARDIAN (Genomic Uniform-screening Against Rare Diseases In All Newborns), will screen newborn babies for 250 rare diseases that are generally not tested for.

The GUARDIAN program will “drive earlier diagnosis and treatment to improve the health of the babies who participate, generate evidence to support the expansion of newborn screening through genomic sequencing, and characterize the prevalence and natural history of rare genetic conditions,” according to a Sema4 news release.

Robert Green, MD

“The appetite for this is growing. The awareness of this is growing. We all see it as inevitable,” medical geneticist Robert Green, MD, at Brigham and Women’s Hospital and Harvard Medical School told USA Today. “We are grossly underutilizing the life-saving benefits of genetics and we have to get past that.” Clinical laboratory leaders understand the value of early detection of disease and subsequent early treatment. (Photo copyright: Harvard Medical School.)

Improving Health of Babies Through Early Detection of Disease

GUARDIAN aims to use WGS to identify conditions at birth that can affect long-term health and subsequently enhance treatment options and possibly prevent disability or death.

The 250 different diseases GUARDIAN will be screening for typically strike young children. They are mostly rare conditions that:

  • have an onset before five years of age,
  • have a greater than 90% probability of the condition developing based on the genetic result,
  • have effective approaches and treatments that are already available, and/or
  • have a well-established natural history of the condition.

“We’re entering the therapeutic era and leaving the diagnostic era,” Paul Kruszka, MD, Chief Medical Officer at GeneDx told USA Today. “This potentially has the opportunity to change the way we practice medicine, especially in rare disease.”

Some Parents Reluctant to Agree to Genetic Testing

Green and his research team first began analyzing the genetic sequences of newborns back in 2013. They believe the costs of performing infant WGS is worthwhile because it can improve lives. However, Green also recognizes that some parents are reluctant to agree to this type of genetic testing due to concerns regarding privacy and the fear of discovering their baby may have an illness.

“You’ve gone through all this pregnancy and you’re sitting there with a healthy baby (and I’m) offering you the opportunity to find out something that’s devastating and terrifying,” he told USA Today. “How fun is that?”

Green continued. “We can respect people who don’t want to know, but also respect people who do want to know. Some families will say ‘I treasure the precious ignorance.’ Others will say ‘If I could have known, I would have poured my heart and soul into clinical trials or spent more time with the child when she was healthy.’”

WGS Screening Identifies Undiagnosed Illnesses in Newborn’s Family

The scientists also found that performing WGS in newborns can detect diseases in the infants as well as unknown illnesses in the families of those babies. According to Kruszka, many parents often seek a diagnosis for a rare disease present in their children for several years. Since many common diseases develop as a result of certain combinations of genes, if illnesses are diagnosed at birth, it could extradite the treatment process, prevent complications, and provide better health outcomes for patients.

“We are relentlessly focused on accelerating the adoption and use of genomic information to impact the lives of as many people as possible, particularly newborns and children,” said Katherine Stueland, President and CEO, Sema4, in the Sema4 news release. “As the first commercial laboratory to launch a rapid whole genome sequencing offering, to address broad unmet needs for early diagnosis, participation in this study is an important step forward for healthcare and in delivering on our goal to sequence once, analyze forever.”

The study is open to all babies in New York City who are born in a health system that participates in the GUARDIAN program, regardless of their race, income, or health insurance coverage.

“The results from this study will help us understand the true impact sequencing at birth can have on newborns and their families in comparison to the current standard of care, particularly as we’ll evaluate clinical outcomes in addition to the psychosocial effect on families,” said Kruszka in the Sema4 news release.

Anything that improves the health of newborn babies is a good thing. Regardless of the cost, if DNA analysis can give newborns and their families a better chance at detecting inherited diseases early while clinical laboratory treatment could make a difference, it is worth pursuing.

JP Schlingman

Related Information:

Understanding the Impacts of Newborn Whole Genome Sequencing

Sema4, GeneDx to Provide Whole Genome Sequencing and Interpretation Services for Landmark Genomic Newborn Screening Study

The Story Behind GUARDIAN, a Groundbreaking Newborn Screening Study

Can Gene Sequencing at Birth Prevent Terrible Diseases? Researchers Hope So.

Animal Healthcare Company Zoetis Completes Acquisition of Basepaws, a Company That Sells At-home DNA Testing Kits for Cats

Genetic testing for the health and wellbeing of beloved pets is not unlike clinical laboratory testing to develop personalized treatments for humans

Clinical laboratory professionals know that the same patients who complain about a $10 copay for their own laboratory testing will happily pay veterinarians tons of cash to test and treat their beloved pets. And as genetic testing for humans becomes commonplace, more people are seemingly willing to pay for genetic analyses of their pets as well.

In June, animal health company Zoetis, Inc. announced it had completed the acquisition of pet care genetics company Basepaws. The financial terms of the deal were not disclosed.

California-based Basepaws is a privately-held company that provides pet owners with analytics, genetic tests, and early health risk assessments for their pets through oral microbiome analysis. Founded in 2017, Basepaws was responsible for the creation of the first at-home genetic testing platform for cats.

Basepaws sells easy-to-use genetic testing kits for cats that allow pet owners and veterinarians to better understand an individual pet’s predisposition to certain illnesses and increase the likelihood of early detection and treatment of those diseases.

It’s not unlike the drive toward personalized medicine and genetic testing that is at the core of human precision medicine.

Different Breeds, Different Needs

Basepaws has a slogan: “Different breeds, different needs.” This means, according to their website, each individual cat has a unique composition of genetic traits that can relate to its needs for optimal health and wellbeing. Obviously, this would apply to all pets.

“As a pioneer in pet care genetics, the California-based Basepaws offers easy-to-use genetic screening tools for the early detection of disease risk in pets, as well as individualized breed and health reports that can identify traits, biomarkers, and potential hereditary conditions for pets. Basepaws helps pet owners and veterinarians understand an individual pet’s risk for disease and can lead to more meaningful engagements and increased likelihood of early detection and treatment of disease,” states a Zoetis press release announcing the acquisition.

“The addition of Basepaws will enhance our portfolio in the precision animal health space and inform our future pipeline of pet care innovations,” said Kristin Peck, CEO of Zoetis, in the press release. “Working together, we can continue to provide veterinarians and pet owners with more comprehensive ways to proactively manage the health, wellness, and quality of care for their animals.”

Anna Skaya
“Basepaws and Zoetis both consist of pet lovers with a passion for science, and our mission is to create better and longer lives for our pets through knowledge and data,” Anna Skaya (above), CEO of Basepaws, told ROI-N.J. “We look forward to expanding our business and the impact of our genetic products with the global scale and [research and development] experience of Zoetis, the world leader in animal health. We believe that, together, we can bring the benefits of a more proactive healthcare approach to pet parents around the world.” Genetic testing for optimum pet health is not unlike the drive for personalized clinical laboratory genetic testing for humans. (Photo copyright: Los Angeles Times.)

Test Results for Hundreds of Genetic Disorders and Health Markers

Basepaws currently sells three DNA test kits for felines on their webpage. The current price for an oral health test kit that identifies active signs of dental diseases is $69. Their breed and cat health DNA test kit, which provides results for over 115 known feline genetic markers, is $129. Their most comprehensive testing kit is a whole genome sequencing (WGS) kit which is currently on sale for $399.

After receiving a test kit by mail, the purchaser registers the kit online, takes a single buccal swab from their kitty’s inner cheek, and then mails the sample to Basepaws. Lab personnel then extract the cat’s DNA from the sample and perform quality checks to ensure the sample is acceptable for genetic testing. It takes four to six weeks for consumers to receive test results.

According to the company’s website, Basepaws’ WGS test provides results related to 43 genetic disorders that are represented by 65 health markers. The listing of genetic disorders contained in the Health Marker section of the Basepaws report includes data on:

  • Metabolic disorders,
  • Musculoskeletal and connective tissue disorders,
  • Renal disorders,
  • Cardiovascular disorders,
  • Blood disorders,
  • Eye disorders,
  • Endocrine disorders,
  • Skin disorders, and
  • Autoimmune disorders.

“The Basepaws team has done an amazing job demonstrating how genetic testing and data can improve how we care for the pets in our lives,” Abhay Nayak, Executive Vice President at Zoetis, told ROI-NJ. “With the addition of Basepaws, Zoetis will continue to strengthen our portfolio of products for precision animal health, across genetics, diagnostics, and data analytics for pets and livestock. We are also excited by how Basepaws’ feline genomic and microbiome database will help enhance our [research and development] capabilities and inform the future of our pet care pipeline.”

Zoetis, based in Parsippany, N.J., manufactures vaccines, medicines, clinical laboratory diagnostics, and other technologies for the benefit of companion pets and livestock. The Fortune 500 company generated $7.8 billion in revenue in 2021, according to its website.

American’s Spend Billions Caring for Their Pets

An article in the peer-reviewed journal PLOS One, titled, “Exploratory Content Analysis of Direct-to-Consumer Pet Genomics: What Is Being Marketed and What Are Consumers Saying?” noted that US pet owners spent approximately $103.6 billion on their pets in 2020, with 30% of that amount going towards veterinary care and products.

The article also stated that the global animal genetic testing market was valued at $990 million in 2020 and is only expected to rise.

Thus, spending money keeping our pets healthy is not only a typical element of Americans’ lives, but also a mega-billion-dollar industry. With at-home genetic testing for humans increasing in popularity, it’s likely testing for animals will follow that trend as well.

In the future, some clinical laboratory organizations may want to consider assessing the animal DNA testing market for its potential to be a useful source of new revenue, especially because potential customers will pay cash when they order genetic tests for their dogs and cats.  

JP Schlingman

Related Information:

Zoetis Acquiring Basepaws, Leader in Pet Care Genetics

Zoetis Completes Acquisition of Basepaws, an Innovative Leader in Petcare Genetics, to Strengthen its Portfolio of Precision Animal Health Solutions

Exploratory Content Analysis of Direct-to-consumer Pet Genomics: What is Being Marketed and What Are Consumers Saying?

Scientists Use Thousands of Genetic Markers to Develop Risk Scores for Six Common Diseases: Findings May Have Implications for Clinical Laboratories

Study demonstrates how precision medicine is advancing because of new insights from the use and interpretation of whole-genome sequencing

As part of the Genomic Medicine at Veterans Affairs Study (GenoVA), researchers from Harvard Medical School, Veterans Affairs Boston Healthcare System, and Brigham and Women’s Hospital in Massachusetts used thousands of genetic markers to develop and validate polygenic risk scores (PRS) for six common illnesses. These findings may eventually provide clinical laboratories and anatomic pathology groups with useful biomarkers and diagnostic tests.

The focus of the ongoing GenoVA study is to “determine the clinical effectiveness of polygenic risk score testing among patients at high genetic risk for at least one of six diseases measured by time-to-diagnosis of prevalent or incident disease over 24 months,” according to the National Institutes of Health.   

The scientists used data obtained from 36,423 patients enrolled in the Mass General Brigham Biobank. The six diseases they researched were:

The polygenic scores were then tested among 227 healthy adult patients to determine their risk for the six diseases. The researchers found that:

  • 11% of the patients had a high-risk score for atrial fibrillation,
  • 7% for coronary artery disease,
  • 8% for diabetes, and
  • 6% for colorectal cancer.

Among the subjects used for the study:

  • 15% of the men in the study had a high-risk score for prostate cancer, and
  • 13% of the women in the study had a high score for breast cancer. 

The researchers concluded that the implementation of PRS may help improve disease prevention and management and give doctor’s a way to assess a patient’s risk for these conditions. They published their findings in the journal Nature Medicine, titled, “Development of a Clinical Polygenic Risk Score Assay and Reporting Workflow.”

“We have shown that [medical] laboratory assay development and PRS reporting to patients and physicians are feasible … As the performance of PRS continues to improve—particularly for individuals of underrepresented ancestry groups—the implementation processes we describe can serve as generalizable models for laboratories and health systems looking to realize the potential of PRS for improved patient health,” the researchers wrote.

Using PRS in Clinical Decision Support

Polygenetic risk scores examine multiple genetic markers for risk of certain diseases. A calculation based on hundreds or thousands of these genetic markers could help doctors and patients make personalized treatment decisions, a core tenet of precision medicine.

“As a primary care physician myself, I knew that busy physicians were not going to have time to take an entire course on polygenic risk scores. Instead, we wanted to design a lab report and informational resources that succinctly told the doctor and patient what they need to know to make a decision about using a polygenic risk score result in their healthcare,” epidemiologist Jason Vassy, MD, told The Harvard Gazette. Vassy is Associate Professor, Harvard Medical School at VA Boston Healthcare System and one of the authors of the research.

Jason Vassy, MD
“This is another great example of precision medicine,” Jason Vassy, MD (above), Adjunct Assistant Professor, General Internal Medicine at Boston University School of Medicine, told WebMD. “There’s always been a tantalizing idea that someone’s genetic makeup might help tailor preventative medicine and treatment.” Personalized clinical laboratory testing is increasingly becoming based on an individual’s genetics. (Photo copyright: Harvard Medical School.)

Increasing Diversity of Patients in Genomic Research

The team did encounter some challenges during their analysis. Because most existing genomic research was performed on persons of European descent, the risk scores are less accurate among non-European populations. The researchers for this study addressed this limitation by applying additional statistical methods to qualify accurate PRS calculations across multiple racial groups.

“Researchers must continue working to increase the diversity of patients participating in genomics research,” said Matthew Lebo, PhD, Chief Laboratory Director, Laboratory Molecular Medicine, at Mass General Brigham and one of the authors of the study. “In the meantime, we were heartened to see that we could generate and implement valid genetic scores for patients of diverse backgrounds,” he told The Harvard Gazette.

The team hopes the scores may be utilized in the future to help doctors and patients make better decisions regarding preventative care and screenings.

“It’s easy to say that everyone needs a colonoscopy at age 45,” Vassy told WebMD. “But what if you’re such a low risk that you could put it off for longer? We may get to the point where we understand risk so much that someone may not need one at all.”

Future of PRS in Clinical Decision Making

The scientists plan to enroll more than 1,000 patients in a new program and track them for two years to assess how medical professionals use PRS in clinical care. It is feasible that patients who are at high risk for certain diseases may opt for more frequent screenings or take preventative medicines to mitigate their risk.

“Getting to that point will take time,” Vassy added. “But I can see this type of information playing a role in shared decision making between doctor and patient in the near future.”

The team also established resources and educational materials to assist both doctors and patients in using the scores.

“It’s still very early days for precision prevention,” Vassy noted, “but we have shown it is feasible to overcome some of the first barriers to bringing polygenic risk scores into the clinic.”

More research and studies are needed to prove the effectiveness of using PRS tests in clinical care and determine its role in customized treatment plans based on personal genetics. Nevertheless, pathologists and medical scientists will want to follow the GenoVA study.  

“It is probably most helpful to think of polygenic risk scores as a risk factor for disease, not a diagnostic test or an indication that an individual will certainly develop the disease,” Vassy said. “Most diseases have complex, multifactorial etiologies, and a high polygenic risk score is just one piece of the puzzle.”

Pathologists and clinical laboratory managers may want to stay informed as researchers in the GenoVA study tease new useful diagnostic insights from their ongoing study of the whole human genome. Meanwhile, the GenoVA team is moving forward with the 1,000-patient study with the expectation that this new knowledge may enable earlier and more accurate diagnoses of the health conditions that were the focus of the GenoVA study.

JP Schlingman

Related Information:

Genetic Risk Scores Developed for Six Diseases

Development of a Clinical Polygenic Risk Score Assay and Reporting Workflow

What If You Knew Your Unique Risk for Every Disease?

Polygenic Risk Scores May Assist Decision-making in Primary Care

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