Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders
Abstract Background Psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BIP), major depressive disorder (MDD), attention deficit-hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) are often related to brain development. Both shared and unique biological and neurodevel...
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doaj-35a1a46e443a4205af57500c05f2c7282021-04-02T18:58:38ZengBMCBMC Medical Genomics1755-87942020-12-0113S1111410.1186/s12920-020-00832-8Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disordersYulin Dai0Timothy D. O’Brien1Guangsheng Pei2Zhongming Zhao3Peilin Jia4Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at HoustonCenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at HoustonCenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at HoustonCenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at HoustonCenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at HoustonAbstract Background Psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BIP), major depressive disorder (MDD), attention deficit-hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) are often related to brain development. Both shared and unique biological and neurodevelopmental processes have been reported to be involved in these disorders. Methods In this work, we developed an integrative analysis framework to seek for the sensitive spatiotemporal point during brain development underlying each disorder. Specifically, we first identified spatiotemporal gene co-expression modules for four brain regions three developmental stages (prenatal, birth to 11 years old, and older than 13 years), totaling 12 spatiotemporal sites. By integrating GWAS summary statistics and the spatiotemporal co-expression modules, we characterized the risk genes and their co-expression partners for five disorders. Results We found that SCZ and BIP, ASD and ADHD tend to cluster with each other and keep a distance from other psychiatric disorders. At the gene level, we identified several genes that were shared among the most significant modules, such as CTNNB1 and LNX1, and a hub gene, ATF2, in multiple modules. Moreover, we pinpointed two spatiotemporal points in the prenatal stage with active expression activities and highlighted one postnatal point for BIP. Further functional analysis of the disorder-related module highlighted the apoptotic signaling pathway for ASD and the immune-related and cell-cell adhesion function for SCZ, respectively. Conclusion Our study demonstrated the dynamic changes of disorder-related genes at the network level, shedding light on the spatiotemporal regulation during brain development.https://doi.org/10.1186/s12920-020-00832-8Mental disorderGenome-Wide Association StudyProtein-protein interactionPrenatalCTNNB1LNX1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yulin Dai Timothy D. O’Brien Guangsheng Pei Zhongming Zhao Peilin Jia |
spellingShingle |
Yulin Dai Timothy D. O’Brien Guangsheng Pei Zhongming Zhao Peilin Jia Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders BMC Medical Genomics Mental disorder Genome-Wide Association Study Protein-protein interaction Prenatal CTNNB1 LNX1 |
author_facet |
Yulin Dai Timothy D. O’Brien Guangsheng Pei Zhongming Zhao Peilin Jia |
author_sort |
Yulin Dai |
title |
Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders |
title_short |
Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders |
title_full |
Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders |
title_fullStr |
Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders |
title_full_unstemmed |
Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders |
title_sort |
characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders |
publisher |
BMC |
series |
BMC Medical Genomics |
issn |
1755-8794 |
publishDate |
2020-12-01 |
description |
Abstract Background Psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BIP), major depressive disorder (MDD), attention deficit-hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) are often related to brain development. Both shared and unique biological and neurodevelopmental processes have been reported to be involved in these disorders. Methods In this work, we developed an integrative analysis framework to seek for the sensitive spatiotemporal point during brain development underlying each disorder. Specifically, we first identified spatiotemporal gene co-expression modules for four brain regions three developmental stages (prenatal, birth to 11 years old, and older than 13 years), totaling 12 spatiotemporal sites. By integrating GWAS summary statistics and the spatiotemporal co-expression modules, we characterized the risk genes and their co-expression partners for five disorders. Results We found that SCZ and BIP, ASD and ADHD tend to cluster with each other and keep a distance from other psychiatric disorders. At the gene level, we identified several genes that were shared among the most significant modules, such as CTNNB1 and LNX1, and a hub gene, ATF2, in multiple modules. Moreover, we pinpointed two spatiotemporal points in the prenatal stage with active expression activities and highlighted one postnatal point for BIP. Further functional analysis of the disorder-related module highlighted the apoptotic signaling pathway for ASD and the immune-related and cell-cell adhesion function for SCZ, respectively. Conclusion Our study demonstrated the dynamic changes of disorder-related genes at the network level, shedding light on the spatiotemporal regulation during brain development. |
topic |
Mental disorder Genome-Wide Association Study Protein-protein interaction Prenatal CTNNB1 LNX1 |
url |
https://doi.org/10.1186/s12920-020-00832-8 |
work_keys_str_mv |
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1721550223821504512 |