The role of genes affected by human evolution marker GNA13 in schizophrenia
Numerous variants associated with increased risk for SCZ have undergone positive selection and were associated with human brain development, but which brain regions and developmental stages were influenced by the positive selection for SCZ risk alleles are unclear. We analyzed SCZ using summary stat...
Gespeichert in:
| Veröffentlicht in: | Progress in neuro-psychopharmacology & biological psychiatry 2020-03, Vol.98, p.109764-109764, Article 109764 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 109764 |
|---|---|
| container_issue | |
| container_start_page | 109764 |
| container_title | Progress in neuro-psychopharmacology & biological psychiatry |
| container_volume | 98 |
| creator | Xiang, Bo Yang, Juanjuan Zhang, Jin Yu, Minglan Huang, Chaohua He, Wenying Lei, Wei Chen, Jing Liu, Kezhi |
| description | Numerous variants associated with increased risk for SCZ have undergone positive selection and were associated with human brain development, but which brain regions and developmental stages were influenced by the positive selection for SCZ risk alleles are unclear. We analyzed SCZ using summary statistics from a genome-wide association study (GWAS) from the Psychiatric Genomics Consortium (PGC). Machine-learning scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele has reached fixation) and incomplete selection (loci where a selected allele has not yet reached fixation). Based on the p value of single nucleotide polymorphisms (SNPs) with selection scores in the top 5%, we formed five subgroups: p |
| doi_str_mv | 10.1016/j.pnpbp.2019.109764 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2311645406</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0278584619304282</els_id><sourcerecordid>2311645406</sourcerecordid><originalsourceid>FETCH-LOGICAL-c359t-928a2240443d51150a1310a03a8f2b840f81f33b668b8308ec6e6c4f22bb34923</originalsourceid><addsrcrecordid>eNp9kMFOGzEQhi1ERQLtEyBVPnJJ8Nhex3vgECEKiKhc4Gx5vWPidLPe2tlI9OlrGuiR04xG38zo_wg5BzYHBupyMx_6oRnmnEFdJvVCySMyBb3QM8lBHZMp46WvtFQTcprzhjEGgokTMhGgCq3UlDw8rZGm2CGNnr5gj5la79HtsKXNK12PW9tT3Mdu3IXY061NvzDR259LEDT0NLt1-BOHdcI-2K_ki7ddxm_v9Yw8_7h5ur6brR5v76-Xq5kTVb2b1VxbziWTUrQVQMUsCGCWCas9b7RkXoMXolFKN1owjU6hctJz3jRC1lyckYvD3SHF3yPmndmG7LDrbI9xzIYLACUryVRBxQF1Keac0JshhRLi1QAzbxbNxvyzaN4smoPFsvX9_cHYbLH9v_OhrQBXBwBLzH3AZLIL2DtsQyruTBvDpw_-Ahxvgek</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2311645406</pqid></control><display><type>article</type><title>The role of genes affected by human evolution marker GNA13 in schizophrenia</title><source>Elsevier ScienceDirect Journals Complete - AutoHoldings</source><creator>Xiang, Bo ; Yang, Juanjuan ; Zhang, Jin ; Yu, Minglan ; Huang, Chaohua ; He, Wenying ; Lei, Wei ; Chen, Jing ; Liu, Kezhi</creator><creatorcontrib>Xiang, Bo ; Yang, Juanjuan ; Zhang, Jin ; Yu, Minglan ; Huang, Chaohua ; He, Wenying ; Lei, Wei ; Chen, Jing ; Liu, Kezhi</creatorcontrib><description>Numerous variants associated with increased risk for SCZ have undergone positive selection and were associated with human brain development, but which brain regions and developmental stages were influenced by the positive selection for SCZ risk alleles are unclear. We analyzed SCZ using summary statistics from a genome-wide association study (GWAS) from the Psychiatric Genomics Consortium (PGC). Machine-learning scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele has reached fixation) and incomplete selection (loci where a selected allele has not yet reached fixation). Based on the p value of single nucleotide polymorphisms (SNPs) with selection scores in the top 5%, we formed five subgroups: p < 0.0001, 0.001, 0.01, 0.05, or 0.1. We found that 48 and 29 genes (p < 0.0001) in complete and incomplete selection, respectively, were enrichedfor the transcriptionalco-expressionprofilein theprenatal dorsolateral prefrontal cortex (DFC), inferior parietal cortex (IPC), and ventrolateral prefrontal cortex (VFC). Core genes (GNA13, TBC1D19, and ZMYM4) involved in regulating early brain development were identified in these three brain regions. RNA sequencing for primary cortical neurons that were transfected Gna13 overexpressed lentivirus demonstrated that 135 gene expression levels changed in the Gna13 overexpressed groups compared with the controls. Gene-set analysis identified important associations among common variants of these 13 genes, which were associated with neurodevelopment and putamen volume [p = 0.031; family-wise error correction (FWEC)], SCZ (p = 0.022; FWEC). The study indicate that certain SCZ risk alleles were likely to undergo positive selection during human evolution due to their involvement in the development of prenatal DFC, IPC and VFC, and suggest that SCZ is related to abnormal neurodevelopment.
•Numerous variants associated with increased risk for schizophrenia have undergone positive selection and were associated with human brain development.•The certain schizophrenia risk alleles were likely to undergo positive selection during human evolution.•The abnormal development of prenatal dorsolateral prefrontal cortex, inferior parietal cortex and ventrolateral prefrontal cortex may be associated with schizophrenia.</description><identifier>ISSN: 0278-5846</identifier><identifier>EISSN: 1878-4216</identifier><identifier>DOI: 10.1016/j.pnpbp.2019.109764</identifier><identifier>PMID: 31676466</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><ispartof>Progress in neuro-psychopharmacology & biological psychiatry, 2020-03, Vol.98, p.109764-109764, Article 109764</ispartof><rights>2019 Elsevier Inc.</rights><rights>Copyright © 2019 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-928a2240443d51150a1310a03a8f2b840f81f33b668b8308ec6e6c4f22bb34923</citedby><cites>FETCH-LOGICAL-c359t-928a2240443d51150a1310a03a8f2b840f81f33b668b8308ec6e6c4f22bb34923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.pnpbp.2019.109764$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31676466$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiang, Bo</creatorcontrib><creatorcontrib>Yang, Juanjuan</creatorcontrib><creatorcontrib>Zhang, Jin</creatorcontrib><creatorcontrib>Yu, Minglan</creatorcontrib><creatorcontrib>Huang, Chaohua</creatorcontrib><creatorcontrib>He, Wenying</creatorcontrib><creatorcontrib>Lei, Wei</creatorcontrib><creatorcontrib>Chen, Jing</creatorcontrib><creatorcontrib>Liu, Kezhi</creatorcontrib><title>The role of genes affected by human evolution marker GNA13 in schizophrenia</title><title>Progress in neuro-psychopharmacology & biological psychiatry</title><addtitle>Prog Neuropsychopharmacol Biol Psychiatry</addtitle><description>Numerous variants associated with increased risk for SCZ have undergone positive selection and were associated with human brain development, but which brain regions and developmental stages were influenced by the positive selection for SCZ risk alleles are unclear. We analyzed SCZ using summary statistics from a genome-wide association study (GWAS) from the Psychiatric Genomics Consortium (PGC). Machine-learning scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele has reached fixation) and incomplete selection (loci where a selected allele has not yet reached fixation). Based on the p value of single nucleotide polymorphisms (SNPs) with selection scores in the top 5%, we formed five subgroups: p < 0.0001, 0.001, 0.01, 0.05, or 0.1. We found that 48 and 29 genes (p < 0.0001) in complete and incomplete selection, respectively, were enrichedfor the transcriptionalco-expressionprofilein theprenatal dorsolateral prefrontal cortex (DFC), inferior parietal cortex (IPC), and ventrolateral prefrontal cortex (VFC). Core genes (GNA13, TBC1D19, and ZMYM4) involved in regulating early brain development were identified in these three brain regions. RNA sequencing for primary cortical neurons that were transfected Gna13 overexpressed lentivirus demonstrated that 135 gene expression levels changed in the Gna13 overexpressed groups compared with the controls. Gene-set analysis identified important associations among common variants of these 13 genes, which were associated with neurodevelopment and putamen volume [p = 0.031; family-wise error correction (FWEC)], SCZ (p = 0.022; FWEC). The study indicate that certain SCZ risk alleles were likely to undergo positive selection during human evolution due to their involvement in the development of prenatal DFC, IPC and VFC, and suggest that SCZ is related to abnormal neurodevelopment.
•Numerous variants associated with increased risk for schizophrenia have undergone positive selection and were associated with human brain development.•The certain schizophrenia risk alleles were likely to undergo positive selection during human evolution.•The abnormal development of prenatal dorsolateral prefrontal cortex, inferior parietal cortex and ventrolateral prefrontal cortex may be associated with schizophrenia.</description><issn>0278-5846</issn><issn>1878-4216</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kMFOGzEQhi1ERQLtEyBVPnJJ8Nhex3vgECEKiKhc4Gx5vWPidLPe2tlI9OlrGuiR04xG38zo_wg5BzYHBupyMx_6oRnmnEFdJvVCySMyBb3QM8lBHZMp46WvtFQTcprzhjEGgokTMhGgCq3UlDw8rZGm2CGNnr5gj5la79HtsKXNK12PW9tT3Mdu3IXY061NvzDR259LEDT0NLt1-BOHdcI-2K_ki7ddxm_v9Yw8_7h5ur6brR5v76-Xq5kTVb2b1VxbziWTUrQVQMUsCGCWCas9b7RkXoMXolFKN1owjU6hctJz3jRC1lyckYvD3SHF3yPmndmG7LDrbI9xzIYLACUryVRBxQF1Keac0JshhRLi1QAzbxbNxvyzaN4smoPFsvX9_cHYbLH9v_OhrQBXBwBLzH3AZLIL2DtsQyruTBvDpw_-Ahxvgek</recordid><startdate>20200302</startdate><enddate>20200302</enddate><creator>Xiang, Bo</creator><creator>Yang, Juanjuan</creator><creator>Zhang, Jin</creator><creator>Yu, Minglan</creator><creator>Huang, Chaohua</creator><creator>He, Wenying</creator><creator>Lei, Wei</creator><creator>Chen, Jing</creator><creator>Liu, Kezhi</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20200302</creationdate><title>The role of genes affected by human evolution marker GNA13 in schizophrenia</title><author>Xiang, Bo ; Yang, Juanjuan ; Zhang, Jin ; Yu, Minglan ; Huang, Chaohua ; He, Wenying ; Lei, Wei ; Chen, Jing ; Liu, Kezhi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-928a2240443d51150a1310a03a8f2b840f81f33b668b8308ec6e6c4f22bb34923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xiang, Bo</creatorcontrib><creatorcontrib>Yang, Juanjuan</creatorcontrib><creatorcontrib>Zhang, Jin</creatorcontrib><creatorcontrib>Yu, Minglan</creatorcontrib><creatorcontrib>Huang, Chaohua</creatorcontrib><creatorcontrib>He, Wenying</creatorcontrib><creatorcontrib>Lei, Wei</creatorcontrib><creatorcontrib>Chen, Jing</creatorcontrib><creatorcontrib>Liu, Kezhi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Progress in neuro-psychopharmacology & biological psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiang, Bo</au><au>Yang, Juanjuan</au><au>Zhang, Jin</au><au>Yu, Minglan</au><au>Huang, Chaohua</au><au>He, Wenying</au><au>Lei, Wei</au><au>Chen, Jing</au><au>Liu, Kezhi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of genes affected by human evolution marker GNA13 in schizophrenia</atitle><jtitle>Progress in neuro-psychopharmacology & biological psychiatry</jtitle><addtitle>Prog Neuropsychopharmacol Biol Psychiatry</addtitle><date>2020-03-02</date><risdate>2020</risdate><volume>98</volume><spage>109764</spage><epage>109764</epage><pages>109764-109764</pages><artnum>109764</artnum><issn>0278-5846</issn><eissn>1878-4216</eissn><abstract>Numerous variants associated with increased risk for SCZ have undergone positive selection and were associated with human brain development, but which brain regions and developmental stages were influenced by the positive selection for SCZ risk alleles are unclear. We analyzed SCZ using summary statistics from a genome-wide association study (GWAS) from the Psychiatric Genomics Consortium (PGC). Machine-learning scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele has reached fixation) and incomplete selection (loci where a selected allele has not yet reached fixation). Based on the p value of single nucleotide polymorphisms (SNPs) with selection scores in the top 5%, we formed five subgroups: p < 0.0001, 0.001, 0.01, 0.05, or 0.1. We found that 48 and 29 genes (p < 0.0001) in complete and incomplete selection, respectively, were enrichedfor the transcriptionalco-expressionprofilein theprenatal dorsolateral prefrontal cortex (DFC), inferior parietal cortex (IPC), and ventrolateral prefrontal cortex (VFC). Core genes (GNA13, TBC1D19, and ZMYM4) involved in regulating early brain development were identified in these three brain regions. RNA sequencing for primary cortical neurons that were transfected Gna13 overexpressed lentivirus demonstrated that 135 gene expression levels changed in the Gna13 overexpressed groups compared with the controls. Gene-set analysis identified important associations among common variants of these 13 genes, which were associated with neurodevelopment and putamen volume [p = 0.031; family-wise error correction (FWEC)], SCZ (p = 0.022; FWEC). The study indicate that certain SCZ risk alleles were likely to undergo positive selection during human evolution due to their involvement in the development of prenatal DFC, IPC and VFC, and suggest that SCZ is related to abnormal neurodevelopment.
•Numerous variants associated with increased risk for schizophrenia have undergone positive selection and were associated with human brain development.•The certain schizophrenia risk alleles were likely to undergo positive selection during human evolution.•The abnormal development of prenatal dorsolateral prefrontal cortex, inferior parietal cortex and ventrolateral prefrontal cortex may be associated with schizophrenia.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>31676466</pmid><doi>10.1016/j.pnpbp.2019.109764</doi><tpages>1</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0278-5846 |
| ispartof | Progress in neuro-psychopharmacology & biological psychiatry, 2020-03, Vol.98, p.109764-109764, Article 109764 |
| issn | 0278-5846 1878-4216 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2311645406 |
| source | Elsevier ScienceDirect Journals Complete - AutoHoldings |
| title | The role of genes affected by human evolution marker GNA13 in schizophrenia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T11%3A17%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20role%20of%20genes%20affected%20by%20human%20evolution%20marker%20GNA13%20in%20schizophrenia&rft.jtitle=Progress%20in%20neuro-psychopharmacology%20&%20biological%20psychiatry&rft.au=Xiang,%20Bo&rft.date=2020-03-02&rft.volume=98&rft.spage=109764&rft.epage=109764&rft.pages=109764-109764&rft.artnum=109764&rft.issn=0278-5846&rft.eissn=1878-4216&rft_id=info:doi/10.1016/j.pnpbp.2019.109764&rft_dat=%3Cproquest_cross%3E2311645406%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2311645406&rft_id=info:pmid/31676466&rft_els_id=S0278584619304282&rfr_iscdi=true |