New research by Yale scientists may give new hope to the 2 percent of the population that suffer from brain aneurysms — including Vice President-elect Joe Biden, who nearly died from a ruptured brain aneurysm in 1988.
Fifteen years of hard work, state-of-the-art technology, and international cooperation came to an apex last Sunday, November 9, when Yale researchers published a study identifying three genes that may increase an individual’s risk of developing a brain aneurysm. The study, which will be contained in the journal Nature Genetics, screened DNA samples from 2,100 intracranial aneurysm cases and 8,000 controls.
Aneurisms, or weak points in the blood vessel wall that can swell and burst, affect approximately 30,000 people per year. The disease has an alarming mortality rate — fewer than half survive the first bleed. Biden had a close brush with death several months after his campaign for president in 1988, when a ruptured aneurysm knocked him unconscious for eight hours.
The study identified three different regions on the human genome that are associated with an increased risk for developing intracranial aneurisms, said the study’s co-author, Murat Günel, chief of the Neurovascular Surgery Program. Each of these genomic sites was confirmed by researchers from all three of the countries involved in the study — a finding that shows these genes are clearly implicated in the disease, researchers said.
“The cornerstone of good science is to be able to replicate the same result,” said Chris Mason, a co-author and post-doctoral fellow at the Yale Child Study Center.
The study was based upon data collected in Finland, Japan and the Netherlands. Finland and Japan have the highest global incidences of intracranial aneurysms, while all three countries are fairly ethnically homogeneous — which makes it easier to perform genetic analysis on their genomes.
The data, Günel said, also gave rise to a new line of thinking.
“The study allowed us to form a hypothesis that intracranial aneurysms have to do with stem cells and progenitor cells,” Günel said.
In a healthy individual, stem cells, which can differentiate into a variety of cell types, replace damaged cells, but older individuals have fewer to do this task. As a result, diseases like cranial aneurysms are age-related — with the median age for a rupture being 50.
The idea of the study had been in the works for 15 years, he added, but the technology that made it possible has only been around for two years.
To collect the data, scientists used a microarray technology, a grid-like arrangement of computer chips that can sequence DNA. The chips collected 300,000 single nucleotide polymorphisms, single base pairs in the human genome that vary naturally in the human population and that are linked to specific genes.
After the blood samples from around the world were sent to Yale, the necessary sequencing took two months to complete.
“We worked more than five days a week on a regular basis to get this done,” said Shrikant Mane, a co-author and the director of the microarray resource center and deputy director of the Keck Foundation laboratory.
The next step, Günel said, is to discover the pathways in which these genes interact and the proteins their encode. Understanding these mechanisms may help researchers to developed therapies for individuals who possess the disease genes the team has found, he said.
“You can imagine that someday you can take a pill and cure your aneurysm,” he said. “Now that is science fiction, but that is our goal.”