The Mount Sinai Health System this week began an effort to build a large database of genetic patient information that can be studied by researchers — and by a major pharmaceutical company.
The aim is to seek treatments for illnesses ranging from schizophrenia to kidney disease, but the effort to collect genetic information for many patients, collected through routine blood tests, 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, such as Ancestry.com and GEDmatch, have been used by detectives looking for genetic clues that might help them solve ancient crimes.
Large sets of genetic sequences can unlock new insights into many diseases and pave the way for new treatments, according to Mount Sinai researchers. But the only way to compile these research databases is to first convince a large number of people to agree to have their genomes sequenced.
Beyond the search for the next breakthrough drug, the researchers hope that the database, when combined 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 – can affect people’s health.
“It’s really transformative,” said Alexander Charney, a professor at the Icahn School of Medicine at Mount Sinai, who oversees the project.
The health system hopes to eventually build a gene sequence database for 1 million patients, which would mean including about one in 10 New Yorkers. word of the hospital, Karin Eskenazi.
This isn’t Mount Sinai’s first attempt to create a DNA database. Over the past fifteen years, Mount Sinai has been slowly building a biological sample bank, or biobank, called BioMe, with around 50,000 DNA sequences to date. However, the researchers were frustrated by the slowness, which they attribute to the cumbersome process they use to obtain consent and enroll patients: multiple surveys and a lengthy one-on-one discussion with a Mount employee. Sinai which sometimes lasts 20 minutes, according to Dr. Girish Nadkarni of Mount Sinai, who leads the project with Dr. Charney.
Most of this consent process is dropped. Mount Sinai dropped health inquiries and reduced the procedure to watching a short video and providing a signature. This week he began trying to enroll most patients who were receiving blood tests as part of their routine care.
A number of large biobanking programs already exist across the country. But the one the Mount Sinai Health System is looking to build would be the first large-scale one to draw attendees primarily from New York. The program may well mark a shift in the way many New Yorkers think about their genetic information, from something private or unknown to something they’ve donated to research.
The project will involve sequencing large numbers of DNA samples, an undertaking that could cost tens or even hundreds of millions of dollars. To avoid this cost, Mount Sinai has partnered with Regeneron, a major pharmaceutical company, which will do the actual sequencing work. In return, the company will have access to each participant’s genetic sequences and partial medical records, according to the Mount Sinai doctors who run the program. Mount Sinai also intends to share data with other researchers.
Although Mount Sinai researchers have access to anonymized electronic health records of every patient who participates, the data shared with Regeneron will be more limited, according to Mount Sinai. The company can access diagnostics, lab reports and vital signs.
When combined with health records, large sets of genetic data can help researchers search for rare mutations that have a strong association with a certain disease or that may protect against it.
It remains to be seen whether Mount Sinai, one of the city’s largest hospital systems, can meet its goal of enrolling one million patients in the program, which the hospital calls the “Mount Sinai Million Health Discoveries Program.” If so, the resulting database will be among the largest in the nation, alongside one run by the U.S. Department of Veterans Affairs as well as a project run by the National Institutes of Health that has aims to eventually enroll 1 million Americans, although it is currently very short.
(Both of these government projects involve whole genome sequencing, which reveals an individual’s complete DNA composition; the Mount Sinai Project will sequence approximately 1% of each individual’s genome, called the exome.)
Regeneron, which in recent years has become widely known for its effective monoclonal antibody treatment for Covid-19, has sequenced and studied the DNA of around 2 million “volunteer patients”, mainly through collaborations with health systems. and a major biobank in Britain, according to the company.
But the number of patients Mount Sinai hopes to enroll — coupled with their 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 that we will all be able to make are quite different from what is possible until today with smaller studies,” said Dr. Aris Baras, senior vice president at Regeneron.
People of European ancestry are generally overrepresented in genomic datasets, which means, for example, that the genetic tests people undergo for cancer risk are much more sensitive to genetic variants common in cancer patients. white, said Dr. Baras.
“If you’re not of European ancestry, there’s less information about variants and genes and you won’t get as good a genetic test as a result,” Dr Baras said.
The Mount Sinai Health System, which has seven hospitals in New York City, sees about 1.1 million individual patients a year and handles more than 3 million outpatient visits to doctors’ offices. Dr. Charney estimated that the hospital system drew blood from at least 300,000 patients a year, and he expected that many of them would consent to their blood being used for genetic research.
The registration rate for such data collection is generally high – around 80%, he said. “So the calculations are checked. We should be able to reach the million.
Mark Gerstein, professor of biomedical informatics at Yale University, said there is no doubt that genomic datasets are driving great medical discoveries. But he said he still wouldn’t take part in any of them himself, and he urged people to consider whether adding their DNA to a database could ever affect their little ones. -children.
“I tend to be worried,” he said.
Our collective knowledge of mutations and the diseases they are associated with – whether Alzheimer’s disease or schizophrenia – would only increase in the years to come, he said. “If the datasets ever leaked, the information could be used to discriminate children or grandchildren from current participants,” Dr. Gerstein said. They could be teased or denied insurance, he added.
He noted that while the data today is anonymous and secure, that could change. “Securing information over long periods of time becomes much more difficult,” he said, noting that Regeneron might not even exist in 50 years. “The risk of data being hacked over such a long period of time becomes magnified,” he said.
Other doctors encouraged participation, noting that genetic research offered great hope for developing treatments for a range of diseases. Dr. Charney, who will oversee the effort to amass a million sequences, studies schizophrenia. He used Mount Sinai’s existing database to search for a particular genetic variant associated with a psychotic illness.
Of the three patients in the existing Mount Sinai BioMe database with this variant, only one had lifelong severe psychotic illness. “What is it in the genomes of these other two people that somehow protected them, or maybe it was their environment that protected them?” He asked.
His team began calling these patients for additional research. The plan is to take samples of their cells and use gene-editing technology to study the effect of various changes on that particular genetic variant. “Essentially what we’re saying is, ‘what’s schizophrenia in a nutshell?
Wilbert Gibson, 65, is listed in Mount Sinai’s existing genetic database. Healthy until he reached 60, his heart began to fail rapidly, but doctors initially struggled to make a diagnosis. At Mount Sinai, he discovered he had cardiac amyloidosis, in which proteins build up in the heart, reducing its ability to pump blood.
He received a heart transplant. When asked if he would share his genome to help research, he was happy to answer. He was involved in genetic research that identified a genetic variant in people of African descent linked to heart disease. Participating in medical research was the easiest decision to make at the time.
“When you’re in the situation I’m in and you see your heart failing and it’s all happening so fast, you’re going to do it,” he said in an interview in which he credited the doctors. of Mount Sinai for saving his life. life.