The Mount Sinai Health System this week began building a massive database of patient genetic information for researchers — and a major pharmaceutical company — to examine.
The goal is to find treatments for diseases ranging from schizophrenia to kidney disease, but efforts to collect genetic information for many patients, collected during routine blood draws, could also raise privacy concerns.
The data will be anonymized, and Mount Sinai said it has no intention of sharing it with anyone other than researchers. But consumer or genealogical databases full of genetic information, like Ancestry.com and GEDmatch, have been used by detectives looking for genetic clues that might help them solve old crimes.
Huge sets of genetic sequences can provide new insights into many diseases and also pave the way for new treatments, researchers at Mount Sinai say. But the only way to compile these research databases is to first convince large numbers of people to consent to having their genomes sequenced.
Aside from finding the next breakthrough drug, the researchers hope the database, coupled with patients’ medical records, will provide new insights into how the interplay between genetic and socioeconomic factors — such as poverty or exposure to air pollution — affects the health of the population can affect people.
“This is really transformative,” said Alexander Charney, a professor at the Icahn School of Medicine at Mount Sinai who leads the project.
The health system hopes to eventually build a database of genetic sequences for 1 million patients, which would enroll about one in 10 New York City residents. Efforts began this week, said a hospital spokeswoman, Karin Eskenazi.
This isn’t Mount Sinai’s first attempt at building a genetic database. For about 15 years, Mount Sinai has been slowly building a biological sample bank, or biobank called BioMe, with about 50,000 DNA sequences to date. However, the researchers were frustrated by the slow pace, which they attribute to the cumbersome process they use to obtain consent and enroll patients: multiple surveys and a lengthy one-on-one interview, sometimes 20 minutes long, with a Mount Sinai staff member. according to Dr. Girish Nadkarni of Mount Sinai, who co-led the project with Dr. Charney directs.
Most of this approval process falls by the wayside. Mount Sinai has ditched the health surveys and reduced the procedure to watching a short video and providing a signature. This week it began trying to accommodate most of the patients who received blood tests as part of their routine care.
A number of large biobank programs are already in place across the country. But the healthcare system that Mount Sinai Health System hopes to build would be the first large-scale one, attracting participants primarily from New York City. The program may well mark a shift in how many New Yorkers feel about their genetic information, from something private or unknown to something they’ve donated to research.
The project will involve the sequencing of large numbers of DNA samples, an endeavor that could cost tens or even hundreds of millions of dollars. To avoid these costs, Mount Sinai has teamed up with Regeneron, a large pharmaceutical company that is doing the actual sequencing work. In exchange, the company will gain access to each participant’s genetic sequences and partial medical records, according to Mount Sinai doctors who lead the program. Mount Sinai also intends to share data with other researchers.
Although Mount Sinai researchers will have access to anonymized electronic medical records of each participating patient, Mount Sinai said the data shared with Regeneron will be more limited. The company can access diagnoses, laboratory reports and vital signs.
When combined with health records, large genetic datasets can help researchers find rare mutations that are either strongly associated with, or protective of, a particular disease.
It remains to be seen if Mount Sinai, one of the city’s largest hospital systems, can meet its goal of enrolling one million patients in what the hospital calls the Mount Sinai Million Health Discoveries Program. If it does, the resulting database will be among the largest in the country, alongside one run by the US Department of Veterans Affairs and a project run by the National Institutes of Health that aims to eventually reach 1 million Americans to enroll it is far too short at the moment.
(These two government projects involve whole-genome sequencing, which reveals a person’s complete DNA make-up; the Mount Sinai project will sequence about 1 percent of each person’s genome, called the exome.)
Regeneron, which has become widely known in recent years for its effective monoclonal antibody treatment against Covid-19, has sequenced and screened the DNA of about 2 million “voluntary patients”, mainly through collaborations with healthcare systems and a major biobank in the UK, it said the enterprise.
But the number of patients Mount Sinai is willing to accept — coupled with its racial and ethnic diversity and that of New York City in general — would set it apart from most existing databases.
“The scale and type of discoveries we can all make is very different than what’s possible with smaller studies to date,” said Dr. Aris Baras, senior vice president at Regeneron.
People of European descent tend to be overrepresented in genomic datasets, which means, for example, genetic testing people who are at risk of cancer receive is much better matched to genetic variants that are common in patients with white cancer, said Dr. Baras.
“If you’re not of European descent, there’s less information about variants and genes, and you won’t get as good a genetic test as a result,” said Dr. Baras.
The Mount Sinai Health System, which has seven hospitals in New York City, treats approximately 1.1 million unique patients annually and performs more than 3 million outpatient visits to physician offices. dr Charney estimated that the hospital system drew blood from at least 300,000 patients annually, and he expected that many of them would consent to having their blood used for genetic research.
The enrollment rate for such data collection is usually high — about 80 percent, he said. “So the math works. We should be able to reach a million.”
Mark Gerstein, a professor of biomedical informatics at Yale University, said there is no question that genomic datasets are driving major medical discoveries. But he said he still wouldn’t take part in one himself, and he urged people to consider whether adding their DNA to a database could one day affect their grandchildren.
“I tend to worry,” he said.
Our collective knowledge of mutations and what diseases they’re associated with — whether Alzheimer’s or schizophrenia — would only increase in the years to come, he said. “If the records are eventually leaked, the information could be used to discriminate against the children or grandchildren of current participants,” said Dr. Gerstein. They could be teased or denied insurance, he added.
He noted that even if the data were anonymous and secure today, that could change. “Securing the information over long periods of time becomes much more difficult,” he said, noting that Regeneron may not even exist in 50 years. “The risk of the data being hacked over such a long period of time becomes greater,” he said.
Other doctors urged participation, noting that genetic research offers great hope for the development of treatments for a range of diseases. dr Charney, who will oversee efforts to amass one million sequences, studies schizophrenia. He used Mount Sinai’s existing database to search for a specific gene variant linked to psychotic illness.
Of the three patients in the existing Mount Sinai BioMe database with this variant, only one had a severe lifelong psychotic illness. “What is it about the genomes of these two other people that protected them in some way, or maybe it’s their environment that protected them?” he asked.
His team has begun inviting these patients for further investigation. The plan is to take samples of their cells and use gene editing technology to study the effects of different changes to that particular genetic variant. “Essentially we’re saying, ‘What is schizophrenia in a court?'” In trying to answer that question, Dr. Charney, “can help you refine the actual disease process.”
Wilbert Gibson, 65, is listed in Mount Sinai’s existing genetic database. Healthy until he was 60, his heart began to fail rapidly, but doctors initially had trouble making a diagnosis. At Mount Sinai, he discovered he had cardiac amyloidosis, a condition in which proteins build up in the heart and reduce its ability to pump blood.
He received a heart transplant. When asked if he would share his genome to help research, he happily agreed. He became involved in genetic research that helped identify a gene variant in people of African descent that has been linked to heart disease. Getting involved in medical research was the easiest decision he faced at the time.
“If you’re in the situation I’m in and you find your heart failing and it’s all happening so fast, go and do it,” he said in an interview, attributing it to the doctors at Mount Sinai, that they had saved his life.