Integrative omics of schizophrenia: from genetic determinants to clinical classification and risk prediction

Guan, Fanglin; Ni, Tong; Zhu, Weili; Williams, L. Keoki; Cui, Long‐Biao; Li, Ming; Tubbs, Justin D.; Sham, Pak-Chung; Gui, Hongsheng

doi:10.1038/s41380-021-01201-2

Cited by 46 publications

(30 citation statements)

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“…With the development of biotechnology, such as sequencing, genetic association analyses and multi-omics integrative analyses can help reveal the pathogenesis of complex diseases [ 36 – 39 ] and provide promising therapeutic candidates for the development of new drugs [ 40 , 41 ]. Therefore, sequencing-based integrative analysis might be a promising direction for determining the genetic architectures of GZMB on the susceptibility of keloids in the future.…”

Section: Discussionmentioning

confidence: 99%

Expression of the GZMB Gene Polymorphism, SNP rs8192917, in 990 Han Chinese Patients with Postoperative Keloids

Wen

Hao³

et al. 2022

Med Sci Monit

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Background A keloid is a pathological scar hyperplasia that is affected by genetic and environmental factors. Although the involvement of cytotoxic granzyme B in keloids has been recognized, there is almost no research on granzyme B ( GZMB) gene polymorphisms and keloids. This study aimed to explore the relationship between genetic polymorphisms of GZMB and postsurgical keloid susceptibility in the Han Chinese population. Material/Methods A total of 3078 participants, including 990 patients with postsurgical keloids and 2088 controls without postsurgical keloids, were enrolled. We selected 15 common DNA variants in the GZMB gene for analysis. Associations were analyzed in both single marker-based and haplotype-based methods. The Genotype-Tissue Expression database was used to examine the biological significance of the targeted single nucleotide polymorphisms (SNPs). Results SNP rs8192917 was found to be associated with the susceptibility of keloids ( t statistic=4.82, P =1.47×10 −6 ). An increased risk of keloids was significantly associated with the minor allele (C allele) of rs8192917 (odds ratio=1.33; 95% CI=1.18–1.49], P =1.47×10 −6 ). In addition, a significant association was reported for genotypes of rs8192917 and clinical severity of keloids (χ 2 =10.61, P =0.03). Conclusions The results suggested there are significant associations between common genetic variants in GZMB and the susceptibility of postsurgical keloids in the Chinese Han population. These genetic polymorphisms were also related with the severity of postsurgical keloid symptoms in participants with keloids. The current study can contribute to future etiological and clinical research of keloids.

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Section: Discussionmentioning

confidence: 99%

Expression of the GZMB Gene Polymorphism, SNP rs8192917, in 990 Han Chinese Patients with Postoperative Keloids

Wen

Hao³

et al. 2022

Med Sci Monit

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“…In particular, using genetic imaging strategies, especially based on the high-quality images presented by MRI techniques, to investigate the influence of genetic factors on brain phenotypes will help to study schizophrenia in a more integrated perspective. The key of the trans-scale and multiomics research strategy is to synthesize the information of different scales and different disciplines, so as to provide the most comprehensive way to explain the nature of schizophrenia (Guan et al, 2021). A recent review systematically summarizes the application of multi-omics approaches in schizophrenia in terms of pathogenesis, disease typing, clinical grading, risk prediction, and precision interventions (Guan et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…The key of the trans-scale and multiomics research strategy is to synthesize the information of different scales and different disciplines, so as to provide the most comprehensive way to explain the nature of schizophrenia (Guan et al, 2021). A recent review systematically summarizes the application of multi-omics approaches in schizophrenia in terms of pathogenesis, disease typing, clinical grading, risk prediction, and precision interventions (Guan et al, 2021). Compared to the information provided by a single discipline, the combination of genetic data and imaging data can provide us with more comprehensive information.…”

Section: Discussionmentioning

confidence: 99%

“…For example, adolescents in a high-risk state can be screened by identified risk factors for schizophrenia, so as to predict and intervene at early stage in the future for adolescents who may suffer from schizophrenia. Future research will place more emphasis on integrated analysis of information across different dimensions supported by trans-scale and multi-omics technologies (van den Heuvel et al, 2019;Guan et al, 2021). This new trans-scale and multi-omics methods give us unprecedented power to understand the nature of schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

“…Multi-omics analysis is a research strategy of integrative analysis that integrates information between different disciplines. Many disciplines, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and connectomics, have made significant contributions to the study of the pathogenesis of schizophrenia (Guan et al, 2021). The multi-omics analysis strategy can provide a more comprehensive perspective on the exploration of schizophrenia pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Shaping the Trans-Scale Properties of Schizophrenia via Cerebral Alterations on Magnetic Resonance Imaging and Single-Nucleotide Polymorphisms of Coding and Non-Coding Regions

Zhao

Wang

et al. 2021

Front. Hum. Neurosci.

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Schizophrenia is a complex mental illness with genetic heterogeneity, which is often accompanied by alterations in brain structure and function. The neurobiological mechanism of schizophrenia associated with heredity remains unknown. Recently, the development of trans-scale and multi-omics methods that integrate gene and imaging information sheds new light on the nature of schizophrenia. In this article, we summarized the results of brain structural and functional changes related to the specific single-nucleotide polymorphisms (SNPs) in the past decade, and the SNPs were divided into non-coding regions and coding regions, respectively. It is hoped that the relationship between SNPs and cerebral alterations can be displayed more clearly and intuitively, so as to provide fresh approaches for the discovery of potential biomarkers and the development of clinical accurate individualized treatment decision-making.

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Association of Gene Expression and Tremor Network Structure

Welton,

Chew,

Mai

et al. 2024

Movement Disorders

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BackgroundTranscriptomic changes in the essential tremor (ET)–associated cerebello‐thalamo‐cortical “tremor network” and their association to brain structure have not been investigated.ObjectiveThe aim was to characterize molecular changes associated with network‐level imaging‐derived phenotypes (IDP) found in ET.MethodsWe performed an imaging‐transcriptomic study in British adults using imaging‐genome‐wide association study summary statistics (UK Biobank “BIG40” cohort; n = 33,224, aged 40–69 years). We imputed imaging‐transcriptomic associations for 184 IDPs and analyzed functional enrichment of gene modules and aggregate network‐level phenotypes. Validation was performed in cerebellar‐tissue RNA‐sequencing data from ET patients and controls (n = 55).ResultsAmong 237,896 individual predicted gene expression levels for 6063 unique genes/transcripts, we detected 2269 genome‐wide significant associations (Bonferroni P < 2.102e‐7, 0.95%). These were concentrated in intracellular volume fraction measures of white matter pathways and in genes with putative links to tremor (MAPT, ARL17A, KANSL1, SPPL2C, LRRC37A4P, PLEKHM1, and FMNL1). Whole‐tremor‐network cortical thickness was associated with a gene module linked to mitochondrial organization and protein quality control (r = 0.91, P = 2e‐70), whereas white‐gray T1‐weighted magnetic resonance imaging (MRI) contrast in the tremor network was associated with a gene module linked to sphingolipid synthesis and ethanolamine metabolism (r = −0.90, P = 2e‐68). Imputed association effect sizes and RNA‐sequencing log‐fold change in the validation dataset were significantly correlated for cerebellar peduncular diffusion MRI phenotypes, and there was a close overlap of significant associations between both datasets for gray matter phenotypes (χ2 = 6.40, P = 0.006).ConclusionsThe identified genes and processes are potential treatment targets for ET, and our results help characterize molecular changes that could in future be used for patient treatment selection or prognosis prediction. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Integrative omics of schizophrenia: from genetic determinants to clinical classification and risk prediction

Cited by 46 publications

References 171 publications

Expression of the GZMB Gene Polymorphism, SNP rs8192917, in 990 Han Chinese Patients with Postoperative Keloids

Expression of the GZMB Gene Polymorphism, SNP rs8192917, in 990 Han Chinese Patients with Postoperative Keloids

Shaping the Trans-Scale Properties of Schizophrenia via Cerebral Alterations on Magnetic Resonance Imaging and Single-Nucleotide Polymorphisms of Coding and Non-Coding Regions

Association of Gene Expression and Tremor Network Structure

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