As part of a multinational, collaborative effort, researchers from the Icahn School of Medicine at Mount Sinai have helped identify more than 100 locations in the human genome associated with the risk of developing schizophrenia, in the largest genomic study published on any psychiatric disorder to date, conducted with 80,000 people. The findings, published online in Nature, point to biological mechanisms and pathways that may underlie schizophrenia, and could lead to new approaches to treating the disorder, which has seen little innovation in drug development in more than 60 years.
In the genome-wide association study (GWAS), the authors looked at more than 80,000 genetic samples from schizophrenia patients and healthy volunteers and found 108 specific locations in the human genome associated with risk for schizophrenia. Eighty-three of those loci had not previously been linked to the disorder.
The study implicates genes expressed in brain tissue, particularly those related to neuronal and synaptic function. These include genes that are active in pathways controlling synaptic plasticity—a function essential to learning and memory—and pathways governing postsynaptic activity, such as voltage-gated calcium channels, which are involved in signaling between cells in the brain. These newly identified loci may point to additional therapeutic targets.
“The fact that we were able to detect genetic risk factors on this massive scale shows that schizophrenia can be tackled by the same approaches that have already transformed our understanding of other diseases,” says paper co-author Michael O’Donovan, PhD.”The wealth of new findings has the potential to kick-start the development of new treatments in schizophrenia, a process which has stalled for the last 60 years.” Read the study abstract.Read more