Genetic association and meta-analysis of a schizophrenia GWAS variant rs10489202 in East Asian populations

Yang, Yongfeng; Wang, Lu; Li, Lingyi; Li, Wenqiang; Zhang, Yan; Chang, Hong; Xiao, Xiao; Li, Ming; Lv, Luxian

doi:10.1038/s41398-018-0211-x

Cited by 10 publications

(6 citation statements)

References 59 publications

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“…e loss in any subunit results in the destabilization of the MPC complex and thus dysfunction of the MPC complex [20]. Recent GWAS and meta-analysis in East Asian population showed MPC2 variant rs10489202 may be a risk locus for schizophrenia [21][22][23], indicating that expression of MPC2 may play a role in pathogenesis of schizophrenia. Additionally, abnormal MPC function was found in several cancers and contributed proliferation of cancers [20].…”

Section: Discussionmentioning

confidence: 99%

Genetic Profiles Playing Opposite Roles of Pathogenesis in Schizophrenia and Glioma

Wen

Xia²,

et al. 2020

Journal of Oncology

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Background. Patients diagnosed with schizophrenia were found having lower risks to develop cancers, including glioma. Based on this epidemiology, we hypothesized that there were gene profiles playing opposite roles in pathogenesis of schizophrenia and glioma. Methods. Based on GEO datasets and TCGA, key genes of schizophrenia genes on the opposite development of glioma were screened by different expressed genes (DEGs) screening, weighted gene coexpression network analysis (WGCNA), disease-specific survival (DSS), and glioma grading and verified by gene set enrichment analysis (GSEA). Results. First, 612 DEGs were screened from schizophrenia and control brain samples. Second, 134 key genes more specific to schizophrenia were left by WGCNA, with 93 key genes having annotations in TCGA. Third, DSS of glioma helped to find 42 key gene expressions of schizophrenia oppositely associated with survival of glioma. Finally, 24 key genes showed opposite expression trends in schizophrenia and different glioma grading, i.e., the upregulated key genes in schizophrenia expressed increasingly in higher grade glioma, and vice versa. CAMK2D and MPC2 were taken as the examples and evaluated by GSEA, which indeed showed opposite trends in the same pathways of schizophrenia and glioma. Conclusion. This workflow of selecting novel targeted genes which may have opposite roles in pathogenesis of two diseases was firstly and innovatively generated by our team. Some filtered key genes were indeed found by their potential effects in several mechanism studies, indicating our process could be effective to generate novel targeted genes. These 24 key genes may provide potential directions for future biochemical and pharmacotherapeutic research studies.

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Section: Discussionmentioning

confidence: 99%

Genetic Profiles Playing Opposite Roles of Pathogenesis in Schizophrenia and Glioma

Wen

Xia²,

et al. 2020

Journal of Oncology

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“…The selection of these schizophrenia risk variants was mainly based on previous association studies of schizophrenia. The inclusion criteria was as follows: (a) risk variants that have been implicated in recent GWAS or meta-analysis of schizophrenia with the Asian population or the Han Chinese population (Yuan et al, 2012; Li et al, 2017; Liu et al, 2017; Xiao et al, 2017; Yang et al, 2018); (b) minor allele frequency (MAF) ≥5% in the Han Chinese population based on the 1000 Genomes Project database; (c) known or promising importance in neural developments and brain functions related to creativity.…”

Section: Methodsmentioning

confidence: 99%

The Association Between Schizophrenia Risk Variants and Creativity in Healthy Han Chinese Subjects

Wang

Guo²,

Guo

et al. 2019

Front. Psychol.

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Although previous evidence has suggested that there is a genetic link between schizophrenia and creativity, the specific genetic variants that underlie the link are still largely unknown. To further explore the potential genetic link between schizophrenia and creativity, in a sample of 580 healthy Han Chinese subjects, this study aimed to (1) validate the role of Neuregulin 1 (NRG1) rs6994992 (one schizophrenia risk variant that has been previously linked to creativity in the European population) in the relationship between schizophrenia and creativity and (2) explore the associations between 10 other schizophrenia risk variants and creativity. For NRG1 rs6994992, the result validated its association with creativity measures. However, since NRG1 rs6994992 is not a schizophrenia risk variant in the Han Chinese population, the validated association suggested that ethnic difference may exist in the relationship between NRG1 rs6994992, schizophrenia and creativity. For other schizophrenia risk variants, the result only demonstrated a nominal association between ZNF536 rs2053079 and creativity measures which would not survive correction for multiple testing. No association between polygenic risk score for these 10 schizophrenia risk variants and creativity measures was observed. In conclusion, this study provides limited evidence for the associations between these schizophrenia risk variants and creativity in healthy Han Chinese subjects. Future studies are warranted to better understand the potential genetic link between schizophrenia and creativity.

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“…There are also studies showing that MPC disruption may worsen pathology in schizophrenia and Alzheimer’s disease. An intronic MPC2 mutation was positively and significantly correlated with schizophrenia in East Asian populations [ 77 ]; however, an earlier genome-wide association study (GWAS) study of the same single nucleotide polymorphism (SNP) did not find a significant association [ 78 ], possibly due to differences in biostatistical methodology. In an in vitro excitotoxicity model that may inform AD, chemical inhibition of the MPC eliminated the neuroprotective effect of lactate supplementation on glutamate-induced excitotoxicity [ 74 ].…”

Section: The Mpc In Post-development Health and Diseasementioning

confidence: 99%

Mitochondrial Pyruvate Carrier Function in Health and Disease across the Lifespan

Buchanan

Taylor

2020

Biomolecules

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As a nodal mediator of pyruvate metabolism, the mitochondrial pyruvate carrier (MPC) plays a pivotal role in many physiological and pathological processes across the human lifespan, from embryonic development to aging-associated neurodegeneration. Emerging research highlights the importance of the MPC in diverse conditions, such as immune cell activation, cancer cell stemness, and dopamine production in Parkinson’s disease models. Whether MPC function ameliorates or contributes to disease is highly specific to tissue and cell type. Cell- and tissue-specific differences in MPC content and activity suggest that MPC function is tightly regulated as a mechanism of metabolic, cellular, and organismal control. Accordingly, recent studies on cancer and diabetes have identified protein–protein interactions, post-translational processes, and transcriptional factors that modulate MPC function. This growing body of literature demonstrates that the MPC and other mitochondrial carriers comprise a versatile and dynamic network undergirding the metabolism of health and disease.

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Genetic association and meta-analysis of a schizophrenia GWAS variant rs10489202 in East Asian populations

Cited by 10 publications

References 59 publications

Genetic Profiles Playing Opposite Roles of Pathogenesis in Schizophrenia and Glioma

Genetic Profiles Playing Opposite Roles of Pathogenesis in Schizophrenia and Glioma

The Association Between Schizophrenia Risk Variants and Creativity in Healthy Han Chinese Subjects

Mitochondrial Pyruvate Carrier Function in Health and Disease across the Lifespan

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