Xi'an Jiaotong University (XJTU) played an important role in the world's largest study on the schizophrenia genome, the research results of which was recently published in Nature, a leading multidisciplinary science journal with worldwide influence.

Entitled Mapping genomic loci implicates genes and synaptic biology in schizophrenia (Link to the paper: https://www.nature.com/articles/s41586-022-04434-5#MOESM2), the article was the fruit of synergy between a team led by professor Zhu Feng and Ma Jiancang from the First Affiliated Hospital of Xi'an Jiaotong University, the Psychiatric Genomics Consortium (PGC), an international consortium of scientists dedicated to analyses of genetic data, the Broad Institute, a mission-driven community that brings together researchers in science, and a series of prestigious institutions at home and abroad.

The researchers identified 287 common variants associated with schizophrenia by sequencing the genomes of nearly 80,000 individuals with schizophrenia and 240,000 members of the control population.

Through fine mapping and functional genome analysis, it was determined that 120 genes (106 coding genes) were regionally expressed in brain neurons (including excitatory neurons and inhibitory neurons) that mainly involve basic processes related to neuronal function, including synaptic organization, differentiation and transmission.

The research also indicated that schizophrenia is correlated with genes associated with rare disruptive coding variants, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and genes implicated by such variants in neurodevelopmental disorders.

Many inter-individual risk variants are inherited and involve a large number of common alleles, rare copy number variants, and rare coding variants. Previous genome-wide association studies (GWAS) identified 176 genomic loci containing common alleles associated with schizophrenia, but the causal variants driving these associations and the biological consequences of these variants were unknown.

This study has furthered the understanding of the contribution of common variants to schizophrenia.