Integrated Analysis of Summary Statistics to Identify Pleiotropic Genes and Pathways for the Comorbidity of Schizophrenia and Cardiometabolic Disease

Líu, Hao; Sun, Yang; Zhang, Xinxin; Li, Shiyang; Hu, Dong; Xiao, Lei; Chen, Yanghui; Wang, Dao Wen

doi:10.3389/fpsyt.2020.00256

Cited by 27 publications

(18 citation statements)

References 89 publications

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“…For example, all of these genes except TYW5 have been associated with various cancers [ 72 – 77 ], BNIP3L and CD47 have been associated with immune function [ 78 ] or infection [ 79 ], and CHRNA2 and TCF4 have been associated with other neuropsychiatric conditions and substance use [ 80 , 81 ]. GATAD2A has been associated with cardiometabolic disease and type 2 diabetes [ 82 , 83 ], which is pertinent because of the increased risk of metabolic syndrome secondary to the use of atypical antipsychotic medications in patients with schizophrenia [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

What genes are differentially expressed in individuals with schizophrenia? A systematic review

et al. 2022

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Schizophrenia is a severe, complex mental disorder characterized by a combination of positive symptoms, negative symptoms, and impaired cognitive function. Schizophrenia is highly heritable (~80%) with multifactorial etiology and complex polygenic genetic architecture. Despite the large number of genetic variants associated with schizophrenia, few causal variants have been established. Gaining insight into the mechanistic influences of these genetic variants may facilitate our ability to apply these findings to prevention and treatment. Though there have been more than 300 studies of gene expression in schizophrenia over the past 15 years, none of the studies have yielded consistent evidence for specific genes that contribute to schizophrenia risk. The aim of this work is to conduct a systematic review and synthesis of case–control studies of genome-wide gene expression in schizophrenia. Comprehensive literature searches were completed in PubMed, EmBase, and Web of Science, and after a systematic review of the studies, data were extracted from those that met the following inclusion criteria: human case–control studies comparing the genome-wide transcriptome of individuals diagnosed with schizophrenia to healthy controls published between January 1, 2000 and June 30, 2020 in the English language. Genes differentially expressed in cases were extracted from these studies, and overlapping genes were compared to previous research findings from the genome-wide association, structural variation, and tissue-expression studies. The transcriptome-wide analysis identified different genes than those previously reported in genome-wide association, exome sequencing, and structural variation studies of schizophrenia. Only one gene, GBP2, was replicated in five studies. Previous work has shown that this gene may play a role in immune function in the etiology of schizophrenia, which in turn could have implications for risk profiling, prevention, and treatment. This review highlights the methodological inconsistencies that impede valid meta-analyses and synthesis across studies. Standardization of the use of covariates, gene nomenclature, and methods for reporting results could enhance our understanding of the potential mechanisms through which genes exert their influence on the etiology of schizophrenia. Although these results are promising, collaborative efforts with harmonization of methodology will facilitate the identification of the role of genes underlying schizophrenia.

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Section: Discussionmentioning

confidence: 99%

What genes are differentially expressed in individuals with schizophrenia? A systematic review

et al. 2022

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“…We note that we did not correct for the additional multiple testing related to testing two gene boundaries and two different case-control definitions as there is significant overlap between these conditions and these are not independent tests; this approach is common in the field. [56][57][58] The two different populations, however, are independent. If we additionally would have corrected for these two populations in the BH correction, the strongest associations in MAGMA and MAGENTA still remain, and the weaker ones would become insignificant.…”

Section: Discussionmentioning

confidence: 99%

Gene Set Enrichment Analsyes Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy

Sobrin

Susarla

Stanwyck

et al. 2022

American Journal of Ophthalmology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Of the known pathogenic beta coronaviruses, only the SARS-CoV2, MERS-CoV, and HCoV-OC43 viruses possess the FURIN cleavage complex motif. This protease also plays a role in apoptosis, inflammation of the vasculature, and lipid metabolism ( Liu et al, 2020 ).…”

Section: Sars-cov-2 Structural Proteins and Their Roles In Viral Entrymentioning

confidence: 99%

“…Neurotransmission may also be related to the expression of SARS-CoV-2 entry protease FURIN. FURIN was found among several genes linked to comorbidity SCZ and cardiometabolic illness, which gives insight into the etiology of these conditions ( Liu et al, 2020 ). Several studies underscore the importance of furin in the CNS, as it has been linked to Alzheimer’s disease (AD) and SCZ ( Scamuffa et al, 2006 ; Schrode et al, 2019 ; Yang et al, 2020 ).…”

Section: Potential Mechanisms Of Sars-cov-2 Mediated Mental Disordersmentioning

confidence: 99%

Impact of SARS-CoV-2 on Host Factors Involved in Mental Disorders

et al. 2022

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COVID-19, caused by SARS-CoV-2, is a systemic illness due to its multiorgan effects in patients. The disease has a detrimental impact on respiratory and cardiovascular systems. One early symptom of infection is anosmia or lack of smell; this implicates the involvement of the olfactory bulb in COVID-19 disease and provides a route into the central nervous system. However, little is known about how SARS-CoV-2 affects neurological or psychological symptoms. SARS-CoV-2 exploits host receptors that converge on pathways that impact psychological symptoms. This systemic review discusses the ways involved by coronavirus infection and their impact on mental health disorders. We begin by briefly introducing the history of coronaviruses, followed by an overview of the essential proteins to viral entry. Then, we discuss the downstream effects of viral entry on host proteins. Finally, we review the literature on host factors that are known to play critical roles in neuropsychiatric symptoms and mental diseases and discuss how COVID-19 could impact mental health globally. Our review details the host factors and pathways involved in the cellular mechanisms, such as systemic inflammation, that play a significant role in the development of neuropsychological symptoms stemming from COVID-19 infection.

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Integrated Analysis of Summary Statistics to Identify Pleiotropic Genes and Pathways for the Comorbidity of Schizophrenia and Cardiometabolic Disease

Cited by 27 publications

References 89 publications

What genes are differentially expressed in individuals with schizophrenia? A systematic review

What genes are differentially expressed in individuals with schizophrenia? A systematic review

Gene Set Enrichment Analsyes Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy

Impact of SARS-CoV-2 on Host Factors Involved in Mental Disorders

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