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.
Chinese mitten crab (Eriocheir sinensis) is one of the most commercially important aquaculture species in China. The androgenic gland (AG) of crustaceans plays pivotal roles in the regulation of male differentiation and in maintaining the male sexual characteristics. In order to reveal related mechanisms in AG, we compared transcriptomes of AG between proliferation and secretion phase. A total of 72,000 unigenes and 4,027 differentially expressed genes were obtained. Gene ontology enrichment analysis indicated that biological processes and metabolic pathways related to protein synthesis and secretion such as transcription, translation, and signal transduction were significantly enriched. Critical genes such as IAG, SXL, TRA-2, SRY, FTZ-F1, FOXL2, and FEM-1 were identified and potentially involved in maintaining the testis development and spermatogenesis. Ribosomes pathway revealed the cause of insulin-like androgenic gland hormone secretion increase. Three insulin-like receptors were thought to be associated with growth and spermatogenesis. In the neuroactive ligand-receptor interaction pathway, the expression of octopamine receptor, 5-HT receptor 1, and melatonin receptor was significantly changed, which revealed the key regulation mechanism of aggressive and mating behavior of males. Comparative transcriptome analysis provided new insights into the genome-wide molecular mechanisms of AG development and the regulatory mechanisms of male development.
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