Doctors create a DNA database of New Yorkers: why is it needed

The Mount Sinai Health System began work this week to build an extensive database of patient genetic information. New York Times.

The goal is to find treatments for various diseases from schizophrenia to kidney disease. But efforts to collect genetic information about many patients collected during routine blood draws could raise privacy concerns.

The data will be anonymous. Mount Sinai said it does not intend to share them with anyone other than researchers. But consumer or genealogy databases like Ancestry.com and GEDmatch have been used by detectives looking for genetic clues. They used them to solve old crimes.

Mount Sinai researchers say the vast sets of genetic sequences could open up new insights into many diseases, as well as pave the way for new treatments. But the only way to collect these databases is to convince huge numbers of people to agree to have their genomes sequenced.

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In addition to finding a progressive cure, the database, 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.

The health system hopes to eventually assemble a database of genetic sequences for 1 million patients. This would mean including roughly one out of every 10 New Yorkers. According to hospital spokeswoman Karin Eskenazi, work began this week.

This is not Mount Sinai's first attempt at a genetic database.

For about 15 years, Mount Sinai has been building a biological sample bank, or biobank, called BioMe. To date, it has about 50 DNA sequences. However, the researchers were frustrated by the slow pace, which they attribute to the cumbersome process for obtaining consent and registering patients. These are multiple interviews and a lengthy one-on-one conversation with a Mount Sinai employee that sometimes lasts 000 minutes.

Much of this consent process goes by the wayside. Mount Sinai has ditched medical examinations and reduced the procedure to watching a short video and providing a signature. This week they are trying to register the majority of patients who have had blood tests as part of their treatment.

A number of major biobank programs already exist across the country. But the one that the Mount Sinai Health System is aiming to build will be the first large-scale event to be attended primarily by New Yorkers. The program may well mark a shift in how many New Yorkers view their genetic information, from private or unknown to something they've donated to research.

The project will involve sequencing a huge number of DNA samples.

This can cost tens or even hundreds of millions of dollars. To avoid such costs, Mount Sinai has partnered with Regeneron, a major pharmaceutical company, to handle the sequencing work. In return, the company will have access to the genetic sequences and partial medical records of each participant. Mount Sinai also intend to share the data with other researchers.

While Mount Sinai researchers have access to anonymous electronic medical records for each participating patient, the data shared with Regeneron will be more limited. The company can access diagnoses, laboratory reports and vital signs.

When combined with medical records, large genetic datasets can help researchers find rare mutations, or they can protect against them.

It remains to be seen if Mount Sinai, one of the city's largest hospital systems, will be able to meet its goal of enrolling a million patients in the program. If this happens, the resulting database will be one of the largest in the world. And in the country, along with a project run by the US Department of Veterans Affairs, and a project run by the National Institutes of Health that will eventually reach 1 million Americans.

These two government projects include whole genome sequencing, which reveals the complete composition of human DNA. The Mount Sinai project will sequence about 1 percent of each person's genome, called the exome.

The Geisinger Health System in northeast Pennsylvania has also created a database of more than 185 DNA sequences in partnership with Regeneron.

This database has played a role in the discovery of mutations that may protect against obesity and fatty liver disease.

Regeneron, which has become widely known in recent years for its effective treatment of Covid-19 with monoclonal antibodies, has sequenced and studied the DNA of approximately 2 million volunteer patients. Mainly thanks to collaborations with health systems and a major biobank in the UK, according to the company.

But the number of patients that Mount Sinai hopes to register for, combined with their racial and ethnic diversity, as well as the diversity of New York as a whole, will make it stand out from most existing databases.

“The scale and type of discoveries that we all will be able to make is very different from what has been possible to date with research,” said Dr. Aris Baras, senior vice president of Regeneron.

According to Dr. Baras, people of European ancestry tend to be overrepresented in genomic datasets. This means that the genetic tests people get for cancer risk are much more tailored to the genetic variants that are common among white cancer patients.

“If you are not of European origin, then there will be less information about variants and genes. And as a result, you will not get such a good genetic test,” said Dr. Baras.

The Mount Sinai Health System, which has seven hospitals in New York City, sees about 1,1 million patients a year and handles more than 3 million outpatient office visits. Dr. Charney has estimated that the hospital system draws blood from at least 300 patients each year. And he expects many of them to agree to having their blood used for genetic research.

The coverage rate for such data collection is usually high, around 80 percent, he said.

Mark Gerstein, professor of biomedical informatics at Yale University, said there is no doubt that genomic datasets are the driving force behind great medical discoveries.

But he said that he himself still would not participate in it. And he urged people to think about whether adding their DNA to the database might someday affect their grandchildren.

“I am somewhat concerned about this,” he said.

Our collective knowledge of mutations and what diseases they are associated with - whether it's Alzheimer's or schizophrenia - will only increase in the coming years, he says. “If data is ever leaked, this information could be used to discriminate against the children or grandchildren of current members,” Dr. Gerstein said. He added that they could be teased or denied insurance.

He noted that even if the data were anonymous and secure, this could change. “Protecting information for long periods of time is getting a lot more difficult,” he said. And noted that Regeneron may not even exist in 50 years. “The risk of data breaches over such a long period of time increases,” he said.

Other doctors called for participation. And they noted that genetic research gives great hopes for the development of methods for treating a number of diseases.

Dr. Charney, who will lead the million-sequence effort, is studying schizophrenia. He used the existing Mount Sinai database to search for a specific gene variant associated with psychotic illness.

Of the three patients in the existing Mount Sinai biome database with this variant, only one had severe lifelong mental illness. “What is it about the genomes of these other two people that somehow protected them? Or maybe the environment protected them?” - he asked.

His team began calling in these patients for more research. The plan is to take samples of their cells. And then use gene-editing technology to study the effect of various changes on that particular genetic variant. Dr. Charney said, "This could help to understand what the real disease process is."

Wilbert Gibson, 65, is listed in the existing Mount Sinai genetic database.

Being healthy until he was 60 years old. His heart began to fail quickly, the doctors struggled with the diagnosis. At Mount Sinai, he discovered that he was suffering from cardiac amyloidosis, in which a protein builds up in the heart that reduces its ability to pump blood.

He had a heart transplant. When asked if he would share his genome to help research, he happily agreed. It was included in genetic studies that helped identify a gene variant in people of African descent that is associated with heart disease. Participating in medical research was the easiest decision he faced at the time.

"When you're in the situation that I'm in and you find your heart is failing, you go and do it," he said in an interview. He credited Mount Sinai doctors with saving his life.