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The expression there is "power in numbers" can mean many things, but what are the ways this "power" can take shape?
For two researchers at the Krembil Research Institute, the power is the number of research samples – more than 1.1 million from patients and controls – that have helped an international group of scientists identify genetic relationships between 25 common brain disorders.
Senior Scientist Dr. Cathy Barr and Clinical Researcher Dr. Paul Sandor contributed to
this landmark study which was published in the journal
"These findings are very exciting because it had been previously noted with twin studies that there was genetic overlap between disorders, and the research is now leading us to the actual genes that overlap," says Dr. Barr. "Now we know some diseases have more genes in common than others, and the next step is to figure out which ones, and examine them at the molecular level."
Technology to analyze genes has improved
To date, the study of psychiatric illnesses relied heavily on what experts call "observed phenomena" – behaviour and symptoms noted by clinicians which contributed to today's classification of disorders such as schizophrenia, Tourette syndrome, obsessive compulsive disorder (OCD), bipolar disorder, autism spectrum disorder and others.
Based on the number of symptoms displayed by a patient, clinicians could determine a diagnosis and possible treatments, but observed data did little to point to causes for these disorders.
As gene research took off and the technology to analyze them improved, many researchers of psychiatric disorders began genetic investigations in hopes of gleaning insight of the underpinnings of these illnesses.
Both Drs. Barr and Sandor are experts on the genetics of Tourette syndrome, a neurodevelopmental disorder that causes a person to make involuntary movements and sounds. They had been collecting genetic samples from affected patients for decades, looking for genes that created risk for the disorder.
"In Tourette syndrome research, we thought the disorder was passed on through simple heredity – where one gene is passed on – because we had seen multiple generations of people in one family affected with Tourette syndrome," says Dr. Sandor.
"But it was actually difficult to pin down a single gene," he adds. "Now, thanks to the pooling of these samples for this study, we know that Tourette syndrome is actually caused by the interaction of a multiplicity of genes – it could be a dozen or more – and that dose of unfavourable genes also determines whether a patient has a mild, moderate or severe case of Tourette syndrome."
Indeed, it is not solely the findings of the study that are ground breaking, but also the methods that helped produce them – ushering in a new way for researchers to pool their data to advance the science of their field.
The study's findings, though led by researchers at Harvard University, are based on contributions of genetic samples from more than 400 scientists at institutions all over the world. This group, collectively known as the Brainstorm Consortium, is an amalgamation of smaller groups that had slowly been building databases of genetic profiles for a single disease or small group of them, in isolation over many years.
"When molecular genetic research was in its infancy, the technology only allowed us to analyze one gene marker at a time requiring about four weeks for each marker because the molecular methods were very slow," explains Dr. Barr who contributed samples to this current study going back to when she first started her research at UHN in the early 1990s.
"Eventually, we could analyze five genes at a time, and now it's a million at a time," she says. "Today, it takes longer to analyze the data that we get from the testing than it does to actually create it."
Despite this progress, the data from these smaller sample groups wasn't strong enough. This was the initial drive behind forming the consortium: consolidating genetic collections to make stronger samples.
'Ground-breaking achievement' to share this much data
This pooling yielded powerful information. Not only did the consortium find an overlap between psychiatric illnesses – for example, there was significant overlap between attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD) and schizophrenia – but their analysis also determined that neurodegenerative illnesses, such as Alzheimer's and Parkinson's disease, are distinct both from one another and from psychiatric illnesses.
"It is a ground-breaking achievement to have been able to share this amount of data and that is increasingly where the field is moving" says Dr. Sandor.
Though the findings are only the beginning of understanding the genetic risk and expression of brain disorders, they are encouraging. Drs. Barr and Sandor hope to learn more, particularly about Tourette syndrome, as more samples are added to the existing group.
"This study is based on the largest genetic sample we've ever seen for Tourette syndrome, but that was only 4,000 samples," says Dr. Sandor. "In comparison, the sample size for schizophrenia was over 100,000 and they found over 100 genes associated with that illness. So the expectation is as the sample size increases, we'll find more genes which will give us more information."
Eventually, scientists hope a better understanding of these genetic relationships will identify the mechanisms of these illnesses and lead to better treatment and more effective interventions.
"It's an exciting time for this research," says Dr. Barr. "With better technology and bigger samples, I really feel my earlier work will pay off and that this will translate into improved treatments for patients in my lifetime."