Different responses to risperidone treatment in Schizophrenia: a multicenter genome-wide association and whole exome sequencing joint study

• Published in: Translational psychiatry Vol. 12; no. 1; p. 173
• Main Authors: Zhao, Mingzhe, Ma, Jingsong, Li, Mo, Zhu, Wenli, Zhou, Wei, Shen, Lu, Wu, Hao, Zhang, Na, Wu, Shaochang, Fu, Chunpeng, Li, Xianxi, Yang, Ke, Tang, Tiancheng, Shen, Ruoxi, He, Lin, Huai, Cong, Qin, Shengying
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.04.2022; Nature Publishing Group
• Subjects: 45/23; 45/43; 631/208/2489; 692/699/476/1799; Antipsychotic Agents - therapeutic use; Antipsychotics; Behavioral Sciences; Biological Psychology; Genes; Genome-Wide Association Study; Genomes; Humans; Medicine; Medicine & Public Health; Neurosciences; Pharmacotherapy; Psychiatry; Psychotropic drugs; Risperidone - therapeutic use; Schizophrenia; Schizophrenia - chemically induced; Schizophrenia - drug therapy; Schizophrenia - genetics; Whole Exome Sequencing
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/s41398-022-01942-w

Risperidone is routinely used in the clinical management of schizophrenia, but the treatment response is highly variable among different patients. The genetic underpinnings of the treatment response are not well understood. We performed a pharmacogenomic study of the treatment response to risperidone in patients with schizophrenia by using a SNP microarray -based genome-wide association study (GWAS) and whole exome sequencing (WES)-based GWAS. DNA samples were collected from 189 patients for the GWAS and from 222 patients for the WES after quality control in multiple centers of China. Antipsychotic response phenotypes of patients who received eight weeks of risperidone treatment were quantified with percentage change on the Positive and Negative Syndrome Scale (PANSS). The GWAS revealed a significant association between several SNPs and treatment response, such as three GRM7 SNPs (rs141134664, rs57521140, and rs73809055). Gene-based analysis in WES revealed 13 genes that were associated with antipsychotic response, such as GPR12 and MAP2K3 . We did not identify shared loci or genes between GWAS and WES, but association signals tended to cluster into the GPCR gene family and GPCR signaling pathway, which may play an important role in the treatment response etiology. This study may provide a research paradigm for pharmacogenomic research, and these data provide a promising illustration of our potential to identify genetic variants underlying antipsychotic responses and may ultimately facilitate precision medicine in schizophrenia.