Identifying Chronic Disease Risks Through Genetic Research

Through collecting data for the Mass General Brigham Biobank, researchers found that three-quarters of biobank participants carrying genetic risks for cancer and heart disease had never been tested.

The Mass General Brigham Biobank team is a collaborative effort comprising researchers from Mass General Brigham institutions, including Massachusetts General Hospital and Brigham and Women’s Hospital. Since beginning the program, more than 120,000 participants have enrolled in the biobank.

Patients were asked to provide information such as health history, survey responses, and blood samples. Through the biobank, researchers can study how an individual’s health is impacted by her genes as well as social determinants of health.

According to researchers, some participants are now receiving medically actionable genomic findings, including genetic markers that could indicate an increased risk for chronic conditions. The research team’s recently published study examined the lessons they learned from their experience, disclosing actionable genetic results to research participants and transitioning them to clinical and preventive care.

The team returned results to 256 participants, 76.3 percent of whom were unaware that they carried a variant that put them at increased risk.

“Many people have a personal or family health history already documented in their medical record indicating they should have been offered genetic testing but never had it, and there are others who had no family history or symptoms to clinically tip doctors off but still carry a dangerous genetic risk variant,” co-lead author Carrie Blout Zawatsky, MS, CGC said in a press release.

“Our findings demonstrate the lifesaving benefit that genomic screening will bring to patients by identifying individuals who do not know that they are at risk.”

Over 87,000 Biobank participants opted to provide blood samples, and the research team performed genetic analysis on 36,417 samples. The researchers focused on 59 genes for conditions designated by the American College of Medical Genetics and Genomics as medically actionable and only returned variants that could increase risk.

The samples were genotyped, and a subset was also sequenced for comparison. Before notifying patients, the researchers verified the genotyped findings and discovered that 45 percent of these variants were incorrect.

Additionally, genotyping failed to identify 72 percent of the dangerous variants found in the comprehensive sequencing. According to researchers, these findings demonstrated limitations in the genotyping approach. An additional sample clinically confirmed all the variants from the patients before fully disclosing the results. 

“Many biobanks rely on genotyping technology instead of genomic sequencing. Our study shows that genotyping, while a useful tool in research, may miss important results that more comprehensive sequencing detects,” said co-senior author Matthew Lebo, PhD, FACMG, chief laboratory director at the Mass General Brigham Laboratory for Molecular Medicine.

“In this study, confirmation of the genotype findings through sequencing was critically important as it allowed us to filter out false positives.”

Although the team alerted 256 participants that they were carrying actionable genomic results, 38 percent of patients declined to receive the results.

“Millions of individuals around the world have been genotyped or sequenced as part of research studies, but very few of these studies have returned potentially lifesaving information, in part because of confusion over the logistics and cost of doing so,” said co-senior author Robert Green, MD, MPH, a Harvard Medical School professor.

“These data will help other groups planning for the return of genomic results in research and remind us that across the entire health care landscape, we are missing an opportunity to help patients avoid cancer and heart disease by not applying published recommendations for genomic testing.”