Two Genomic Pathways Tagged For Roles In Schizophrenia

University of North Carolina School of Medicine scientists published a genome-wide association study (GWAS) that identifies 22 locations in the human genome thought to be involved in causing schizophrenia. Thirteen of these genomic sites are newly discovered.

"If finding the causes of schizophrenia is like solving a jigsaw puzzle, then these new results give us the corners and some of the pieces on the edges," said study lead author Patrick F. Sullivan, M.D. "We've debated this for a century, and we are now zeroing in on answers.

"This study gives us the clearest picture to date of two different pathways that might be going wrong in people with schizophrenia. Now we need to concentrate our research very urgently on these two pathways in our quest to understand what causes this disabling mental illness."

Dr. Sullivan is a professor in the departments of genetics and psychiatry and director of the Center for Psychiatric Genomics at the University of North Carolina School of Medicine. His team work appears on line in Nature Genetics.

The results are based on a multi-stage analysis that began with a Swedish national sample of 5,001 schizophrenia cases and 6,243 controls, followed by a meta-analysis of previous GWAS studies, and finally by replication of single nucleotide polymorphisms in 168 genomic regions in independent samples. The total number of people in the study was more than 59,000.

One of the two pathways identified by the study, according to Dr. Sullivan, is a calcium channel pathway. This pathway includes the genes CACNA1C and CACNB2, whose proteins touch each other as part of an important process in nerve cells. The other is the "micro-RNA 137," which includes the MIR137 gene (known to regulate neuronal development) and at least a dozen other genes regulated by MIR137.

"What's really exciting about this is that now we can use standard, off-the-shelf genomic technologies to help us fill in the missing pieces," continued Dr. Sullivan. "We now have a clear and obvious path to getting a fairly complete understanding of the genetic part of schizophrenia. That wouldn't have been possible five years ago."

This article was reprinted from Genetic Engineering & Biotechnology News (GEN) with permission from Mary Ann Liebert, Inc., publishers. Genetic Engineering & Biotechnology News (GEN) has retained its position as the number one biotech publisher around the globe since its launch in 1981. GEN publishes a print edition 21 times a year and has additional exclusive editorial content online, like news and analysis as well as blogs, podcasts, webinars, polls, videos, and application notes. GEN's unique news and technology focus includes the entire bioproduct life cycle from early-stage R&D, to applied research including omics, biomarkers, as well as diagnostics, to bioprocessing and commercialization.