Tarjinder Singh, PhD, is a postdoctoral fellow in the lab of Mark Daly, PhD, in the Analytic and Translational Genetics Unit at Massachusetts General Hospital. His poster, The meta-analysis of rare coding variants in the whole-exome sequences of 25,000 cases and 50,000 controls implicates individual risk genes for schizophrenia, was among the winners at this year’s Mass General Scientific Advisory Committee poster session.
Hear more about Singh’s research in his guest blog post below:
Schizophrenia is a severe and potentially debilitating mental illness that affects nearly 1% of the general population. While there are treatments available, they are not often effective in all patients, and only help control some symptoms.
Our limited understanding of the precise biological mechanisms underlying schizophrenia is a key barrier to developing more effective treatments.
It has been shown that schizophrenia, like other mental illnesses studied so far, have varying degrees of genetic contribution. We can leverage this information to discover relevant genes and pathways to improve our understanding of how the condition develops.
To this end, we are working with a large global team of scientists called the Schizophrenia Exome Sequencing Meta-Analysis (SCHEMA) Consortium to compare the protein-coding DNA sequences (or exomes) of people with and without schizophrenia to identify genetic differences in specific genes that contribute to risk.
Our study actively recruited patients and families from diverse global populations, including people of European, Latin American, Asian, Ashkenazi Jewish, and African American ancestry.
After seven years of collaborative effort, we have processed and analyzed the exomes of nearly 25,000 people with schizophrenia and over 50,000 people without schizophrenia, one of the largest of such studies of any disorder to date.
While earlier efforts have already identified common genetic risk factors for schizophrenia, our work is unique in that it leverages DNA sequencing at an unprecedented scale, which enables us to interrogate much rarer genetic changes that are often unique to a single individual and likely carry greater risk. These ultra-rare genetic changes that disrupt individual genes appear to be enriched in people with schizophrenia, and affect genes and pathways linked to synaptic function and brain development. Furthermore, we are also beginning to implicate individual risk genes that, when disrupted, dramatically increase risk for schizophrenia.
By studying what the function of these genes are in follow-up experiments, we may gain new and exciting insights into various biological causes of schizophrenia. While this is only a first step, we feel that this on-going effort will make meaningful contributions to our understanding of schizophrenia and move us in the right direction in improving treatments in the clinic.