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Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs
Combining genome-wide mapping of SNP-rich regions in schizophrenics and gene expression data in all brain compartments across the human life span revealed that genes with promoters most frequently mutated in schizophrenia are expression hubs interacting with far more genes than the rest of the genom...
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| Published in: | Scientific reports 2017-04, Vol.7 (1), p.45494-45494, Article 45494 |
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| creator | Hegyi, Hedi |
| description | Combining genome-wide mapping of SNP-rich regions in schizophrenics and gene expression data in all brain compartments across the human life span revealed that genes with promoters most frequently mutated in schizophrenia are expression hubs interacting with far more genes than the rest of the genome. We summed up the differentially methylated “expression neighbors” of genes that fall into one of 108 distinct schizophrenia-associated loci with high number of SNPs. Surprisingly, the number of expression neighbors of the genes in these loci were
35 times
higher for the positively correlating genes (
32 times
higher for the negatively correlating ones) than for the rest of the ~16000 genes. While the genes in the 108 loci have little known impact in schizophrenia, we identified many more known schizophrenia-related important genes with a high degree of connectedness (e.g.
MOBP, SYNGR1
and
DGCR6
), validating our approach. Both the most connected positive and negative hubs affected synapse-related genes the most, supporting the synaptic origin of schizophrenia. At least half of the top genes in both the correlating and anti-correlating categories are cancer-related, including oncogenes (
RRAS
and
ALDOA
), providing further insight into the observed inverse relationship between the two diseases. |
| doi_str_mv | 10.1038/srep45494 |
| format | article |
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35 times
higher for the positively correlating genes (
32 times
higher for the negatively correlating ones) than for the rest of the ~16000 genes. While the genes in the 108 loci have little known impact in schizophrenia, we identified many more known schizophrenia-related important genes with a high degree of connectedness (e.g.
MOBP, SYNGR1
and
DGCR6
), validating our approach. Both the most connected positive and negative hubs affected synapse-related genes the most, supporting the synaptic origin of schizophrenia. At least half of the top genes in both the correlating and anti-correlating categories are cancer-related, including oncogenes (
RRAS
and
ALDOA
), providing further insight into the observed inverse relationship between the two diseases.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep45494</identifier><identifier>PMID: 28382934</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/114/116 ; 631/378/116 ; 631/553/2703 ; 631/553/2710 ; 692/699/476/1799 ; Brain - metabolism ; Cancer ; DNA Methylation ; Extracellular Matrix Proteins - genetics ; Extracellular Matrix Proteins - metabolism ; Gene expression ; Gene mapping ; Gene Regulatory Networks - genetics ; Genetic Loci ; Genomes ; Humanities and Social Sciences ; Humans ; Life span ; Mental disorders ; multidisciplinary ; Myelin ; Myelin Proteins - genetics ; Myelin Proteins - metabolism ; Oligodendrocyte-myelin glycoprotein ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Promoters ; Schizophrenia ; Schizophrenia - genetics ; Schizophrenia - pathology ; Science ; Single-nucleotide polymorphism ; Synapses ; Synapses - metabolism ; Synaptogyrins - genetics ; Synaptogyrins - metabolism</subject><ispartof>Scientific reports, 2017-04, Vol.7 (1), p.45494-45494, Article 45494</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Apr 2017</rights><rights>Copyright © 2017, The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-d80166eabfa0dd6ddb77b044a80d8e14e192706e5bb051266057f983b22b643b3</citedby><cites>FETCH-LOGICAL-c438t-d80166eabfa0dd6ddb77b044a80d8e14e192706e5bb051266057f983b22b643b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1903457581/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1903457581?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28382934$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hegyi, Hedi</creatorcontrib><title>Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Combining genome-wide mapping of SNP-rich regions in schizophrenics and gene expression data in all brain compartments across the human life span revealed that genes with promoters most frequently mutated in schizophrenia are expression hubs interacting with far more genes than the rest of the genome. We summed up the differentially methylated “expression neighbors” of genes that fall into one of 108 distinct schizophrenia-associated loci with high number of SNPs. Surprisingly, the number of expression neighbors of the genes in these loci were
35 times
higher for the positively correlating genes (
32 times
higher for the negatively correlating ones) than for the rest of the ~16000 genes. While the genes in the 108 loci have little known impact in schizophrenia, we identified many more known schizophrenia-related important genes with a high degree of connectedness (e.g.
MOBP, SYNGR1
and
DGCR6
), validating our approach. Both the most connected positive and negative hubs affected synapse-related genes the most, supporting the synaptic origin of schizophrenia. At least half of the top genes in both the correlating and anti-correlating categories are cancer-related, including oncogenes (
RRAS
and
ALDOA
), providing further insight into the observed inverse relationship between the two diseases.</description><subject>631/114/116</subject><subject>631/378/116</subject><subject>631/553/2703</subject><subject>631/553/2710</subject><subject>692/699/476/1799</subject><subject>Brain - metabolism</subject><subject>Cancer</subject><subject>DNA Methylation</subject><subject>Extracellular Matrix Proteins - genetics</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>Gene expression</subject><subject>Gene mapping</subject><subject>Gene Regulatory Networks - genetics</subject><subject>Genetic Loci</subject><subject>Genomes</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Life span</subject><subject>Mental disorders</subject><subject>multidisciplinary</subject><subject>Myelin</subject><subject>Myelin Proteins - genetics</subject><subject>Myelin Proteins - metabolism</subject><subject>Oligodendrocyte-myelin glycoprotein</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Promoter Regions, Genetic</subject><subject>Promoters</subject><subject>Schizophrenia</subject><subject>Schizophrenia - genetics</subject><subject>Schizophrenia - pathology</subject><subject>Science</subject><subject>Single-nucleotide polymorphism</subject><subject>Synapses</subject><subject>Synapses - metabolism</subject><subject>Synaptogyrins - genetics</subject><subject>Synaptogyrins - metabolism</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNplkVFrFDEUhYNYbKl98A9IwBcrjE0yyUzmRZDF2kJpC63PIZnc2UmZTcZkxrr99c2ydVn1vuTC-Tg5yUHoHSWfKSnlWYowcsEb_godMcJFwUrGXu_th-gkpQeSR7CG0-YNOmSylKwp-RHqFsF7aCfnl3i1hsH5IsKgJ7BYe4vT2utxci2269TNPnPBY-dxanv3FMY-gncaP7qpx3fXt0V0bY-X4AHD7zFCShu8n016iw46PSQ4eTmP0Y_zb_eLi-Lq5vvl4utV0fJSToWVhFYVaNNpYm1lralrQzjXklgJlANtWE0qEMYQQVlVEVF3jSwNY6bipSmP0Zet7zibFdgW_BT1oMboVjquVdBO_a1416tl-KVE_hDBWTb4-GIQw88Z0qRWLrUwDNpDmJOiUnIpK9qQjH74B30Ic_T5eWojc1ELSTN1uqXaGFLuqtuFoURtClS7AjP7fj_9jvxTVwY-bYGUJb-EuHflf27Pb2KmdQ</recordid><startdate>20170406</startdate><enddate>20170406</enddate><creator>Hegyi, Hedi</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170406</creationdate><title>Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs</title><author>Hegyi, Hedi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-d80166eabfa0dd6ddb77b044a80d8e14e192706e5bb051266057f983b22b643b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>631/114/116</topic><topic>631/378/116</topic><topic>631/553/2703</topic><topic>631/553/2710</topic><topic>692/699/476/1799</topic><topic>Brain - metabolism</topic><topic>Cancer</topic><topic>DNA Methylation</topic><topic>Extracellular Matrix Proteins - genetics</topic><topic>Extracellular Matrix Proteins - metabolism</topic><topic>Gene expression</topic><topic>Gene mapping</topic><topic>Gene Regulatory Networks - genetics</topic><topic>Genetic Loci</topic><topic>Genomes</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Life span</topic><topic>Mental disorders</topic><topic>multidisciplinary</topic><topic>Myelin</topic><topic>Myelin Proteins - genetics</topic><topic>Myelin Proteins - metabolism</topic><topic>Oligodendrocyte-myelin glycoprotein</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Promoter Regions, Genetic</topic><topic>Promoters</topic><topic>Schizophrenia</topic><topic>Schizophrenia - genetics</topic><topic>Schizophrenia - pathology</topic><topic>Science</topic><topic>Single-nucleotide polymorphism</topic><topic>Synapses</topic><topic>Synapses - metabolism</topic><topic>Synaptogyrins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hegyi, Hedi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-04-06</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>45494</spage><epage>45494</epage><pages>45494-45494</pages><artnum>45494</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Combining genome-wide mapping of SNP-rich regions in schizophrenics and gene expression data in all brain compartments across the human life span revealed that genes with promoters most frequently mutated in schizophrenia are expression hubs interacting with far more genes than the rest of the genome. We summed up the differentially methylated “expression neighbors” of genes that fall into one of 108 distinct schizophrenia-associated loci with high number of SNPs. Surprisingly, the number of expression neighbors of the genes in these loci were
35 times
higher for the positively correlating genes (
32 times
higher for the negatively correlating ones) than for the rest of the ~16000 genes. While the genes in the 108 loci have little known impact in schizophrenia, we identified many more known schizophrenia-related important genes with a high degree of connectedness (e.g.
MOBP, SYNGR1
and
DGCR6
), validating our approach. Both the most connected positive and negative hubs affected synapse-related genes the most, supporting the synaptic origin of schizophrenia. At least half of the top genes in both the correlating and anti-correlating categories are cancer-related, including oncogenes (
RRAS
and
ALDOA
), providing further insight into the observed inverse relationship between the two diseases.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28382934</pmid><doi>10.1038/srep45494</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2017-04, Vol.7 (1), p.45494-45494, Article 45494 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5382542 |
| source | Publicly Available Content Database; PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 631/114/116 631/378/116 631/553/2703 631/553/2710 692/699/476/1799 Brain - metabolism Cancer DNA Methylation Extracellular Matrix Proteins - genetics Extracellular Matrix Proteins - metabolism Gene expression Gene mapping Gene Regulatory Networks - genetics Genetic Loci Genomes Humanities and Social Sciences Humans Life span Mental disorders multidisciplinary Myelin Myelin Proteins - genetics Myelin Proteins - metabolism Oligodendrocyte-myelin glycoprotein Polymorphism, Single Nucleotide Promoter Regions, Genetic Promoters Schizophrenia Schizophrenia - genetics Schizophrenia - pathology Science Single-nucleotide polymorphism Synapses Synapses - metabolism Synaptogyrins - genetics Synaptogyrins - metabolism |
| title | Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs |
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