FOLLOWING UP ON EARLIER WORK that identified three gene locations that may be implicated in schizophrenia, researchers at UCLA and colleagues from around the world now have identified additional genes that confirm what scientists have long suspected – that the immune system may play a role in the development of the disorder. Further, they have also identified genetic anomalies that disrupt the cellular pathways involved in brain development, memory and cognition, all markers of schizophrenia. The research was published online in Nature.
Roel Ophoff, Ph.D., associate professor at the Center for Neurobehavioral Genetics at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, and collaborators from nearly 50 institutions worldwide performed a genome-wide scan of 2,663 people diagnosed with schizophrenia and 13,498 controls from eight European locations. They were looking for single nucleotide polymorphisms, genetic variations that are commonly present in the general population but more often present in those suffering from the disorder. They found significant associations with genetic markers on the Major Histocompatibility Complex, a group of genes that controls several aspects of the immune response. Further, they discovered additional variations in two other genes, called NRGN and TCF4, which points to perturbation of pathways involved in brain development, memory and cognition.
“This is another step forward in understanding the biological basis of this disorder,” Dr. Ophoff says. “It also shows the importance of worldwide collaborations for the study of schizophrenia genetics.”
The findings are significant, yet not without challenge, says Dr. Ophoff, since the study aimed at the “common variants” in the human genome. “In other words, these are not rare mutations present in only a few individuals, but these genetic variants are abundantly present in the population,” he says. “Anybody could carry this variant, but that doesn’t mean they will necessarily develop the disease. Yet, when you look at the population at large, these variants are more often present in patients than in healthy control subjects.”
And that’s important, he noted, in developing new techniques to thwart the disease. “Knowing these specific genes are involved in the pathway leading to schizophrenia provides unique clues as to which molecular mechanisms are involved,” Dr. Ophoff says.