High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors
To date, no large scale, systematic description of the blood serum proteome has been performed in inflammatory bowel disease (IBD) patients. By using microarray technology, a more complete description of the blood proteome of IBD patients is feasible. It may help to achieve a better understanding of...
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| creator | Di Narzo, Antonio F Telesco, Shannon E Brodmerkel, Carrie Argmann, Carmen Peters, Lauren A Li, Katherine Kidd, Brian Dudley, Joel Cho, Judy Schadt, Eric E Kasarskis, Andrew Dobrin, Radu Hao, Ke |
| description | To date, no large scale, systematic description of the blood serum proteome has been performed in inflammatory bowel disease (IBD) patients. By using microarray technology, a more complete description of the blood proteome of IBD patients is feasible. It may help to achieve a better understanding of the disease. We analyzed blood serum profiles of 1128 proteins in IBD patients of European descent (84 Crohn's Disease (CD) subjects and 88 Ulcerative Colitis (UC) subjects) as well as 15 healthy control subjects, and linked protein variability to patient age (all cohorts) and genetic components (genotype data generated from CD patients). We discovered new, previously unreported aging-associated proteomic traits (such as serum Albumin level), confirmed previously reported results from different tissues (i.e., upregulation of APOE with aging), and found loss of regulation of MMP7 in CD patients. In carrying out a genome wide genotype-protein association study (proteomic Quantitative Trait Loci, pQTL) within the CD patients, we identified 41 distinct proteomic traits influenced by cis pQTLs (underlying SNPs are referred to as pSNPs). Significant overlaps between pQTLs and cis eQTLs corresponding to the same gene were observed and in some cases the QTL were related to inflammatory disease susceptibility. Importantly, we discovered that serum protein levels of MST1 (Macrophage Stimulating 1) were regulated by SNP rs3197999 (p = 5.96E-10, FDR |
| doi_str_mv | 10.1371/journal.pgen.1006565 |
| format | Article |
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By using microarray technology, a more complete description of the blood proteome of IBD patients is feasible. It may help to achieve a better understanding of the disease. We analyzed blood serum profiles of 1128 proteins in IBD patients of European descent (84 Crohn's Disease (CD) subjects and 88 Ulcerative Colitis (UC) subjects) as well as 15 healthy control subjects, and linked protein variability to patient age (all cohorts) and genetic components (genotype data generated from CD patients). We discovered new, previously unreported aging-associated proteomic traits (such as serum Albumin level), confirmed previously reported results from different tissues (i.e., upregulation of APOE with aging), and found loss of regulation of MMP7 in CD patients. In carrying out a genome wide genotype-protein association study (proteomic Quantitative Trait Loci, pQTL) within the CD patients, we identified 41 distinct proteomic traits influenced by cis pQTLs (underlying SNPs are referred to as pSNPs). Significant overlaps between pQTLs and cis eQTLs corresponding to the same gene were observed and in some cases the QTL were related to inflammatory disease susceptibility. Importantly, we discovered that serum protein levels of MST1 (Macrophage Stimulating 1) were regulated by SNP rs3197999 (p = 5.96E-10, FDR<5%), an accepted GWAS locus for IBD. Filling the knowledge gap of molecular mechanisms between GWAS hits and disease susceptibility requires systematically dissecting the impact of the locus at the cell, mRNA expression, and protein levels. The technology and analysis tools that are now available for large-scale molecular studies can elucidate how alterations in the proteome driven by genetic polymorphisms cause or provide protection against disease. Herein, we demonstrated this directly by integrating proteomic and pQTLs with existing GWAS, mRNA expression, and eQTL datasets to provide insights into the biological processes underlying IBD and pinpoint causal genetic variants along with their downstream molecular consequences.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1006565</identifier><identifier>PMID: 28129359</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aging ; Aging (Biology) ; Aging - blood ; Analysis ; Biology ; Biology and Life Sciences ; Biomarkers - blood ; Case-Control Studies ; Crohn's disease ; Crohns disease ; Disease susceptibility ; Female ; Genes ; Genetic aspects ; Genetic polymorphisms ; Genetic Predisposition to Disease ; Genetics ; Genomes ; Genomics ; Genotype & phenotype ; Health aspects ; Hepatocyte Growth Factor - blood ; High-Throughput Screening Assays ; Humans ; Inflammatory bowel disease ; Inflammatory bowel diseases ; Inflammatory Bowel Diseases - blood ; Inflammatory Bowel Diseases - epidemiology ; Inflammatory Bowel Diseases - genetics ; Male ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Polymorphism, Single Nucleotide ; Protein expression ; Proteins ; Proteome - genetics ; Proteome - metabolism ; Proteomics ; Proto-Oncogene Proteins - blood ; Quantitative Trait Loci</subject><ispartof>PLoS genetics, 2017-01, Vol.13 (1), p.e1006565-e1006565</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Di Narzo AF, Telesco SE, Brodmerkel C, Argmann C, Peters LA, Li K, et al. (2017) High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors. PLoS Genet 13(1): e1006565. doi:10.1371/journal.pgen.1006565</rights><rights>2017 Di Narzo et al 2017 Di Narzo et al</rights><rights>2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Di Narzo AF, Telesco SE, Brodmerkel C, Argmann C, Peters LA, Li K, et al. (2017) High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors. PLoS Genet 13(1): e1006565. doi:10.1371/journal.pgen.1006565</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c759t-b76dcb3bd6be5a58280e438ca3bcb241ead204527cf78ed0703270f86dcb74463</citedby><cites>FETCH-LOGICAL-c759t-b76dcb3bd6be5a58280e438ca3bcb241ead204527cf78ed0703270f86dcb74463</cites><orcidid>0000-0003-2110-1145 ; 0000-0002-1578-5029 ; 0000-0002-3336-0091 ; 0000-0002-3747-0474 ; 0000-0002-4033-5038</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5271178/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5271178/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28129359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Barsh, Gregory S.</contributor><creatorcontrib>Di Narzo, Antonio F</creatorcontrib><creatorcontrib>Telesco, Shannon E</creatorcontrib><creatorcontrib>Brodmerkel, Carrie</creatorcontrib><creatorcontrib>Argmann, Carmen</creatorcontrib><creatorcontrib>Peters, Lauren A</creatorcontrib><creatorcontrib>Li, Katherine</creatorcontrib><creatorcontrib>Kidd, Brian</creatorcontrib><creatorcontrib>Dudley, Joel</creatorcontrib><creatorcontrib>Cho, Judy</creatorcontrib><creatorcontrib>Schadt, Eric E</creatorcontrib><creatorcontrib>Kasarskis, Andrew</creatorcontrib><creatorcontrib>Dobrin, Radu</creatorcontrib><creatorcontrib>Hao, Ke</creatorcontrib><title>High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>To date, no large scale, systematic description of the blood serum proteome has been performed in inflammatory bowel disease (IBD) patients. By using microarray technology, a more complete description of the blood proteome of IBD patients is feasible. It may help to achieve a better understanding of the disease. We analyzed blood serum profiles of 1128 proteins in IBD patients of European descent (84 Crohn's Disease (CD) subjects and 88 Ulcerative Colitis (UC) subjects) as well as 15 healthy control subjects, and linked protein variability to patient age (all cohorts) and genetic components (genotype data generated from CD patients). We discovered new, previously unreported aging-associated proteomic traits (such as serum Albumin level), confirmed previously reported results from different tissues (i.e., upregulation of APOE with aging), and found loss of regulation of MMP7 in CD patients. In carrying out a genome wide genotype-protein association study (proteomic Quantitative Trait Loci, pQTL) within the CD patients, we identified 41 distinct proteomic traits influenced by cis pQTLs (underlying SNPs are referred to as pSNPs). Significant overlaps between pQTLs and cis eQTLs corresponding to the same gene were observed and in some cases the QTL were related to inflammatory disease susceptibility. Importantly, we discovered that serum protein levels of MST1 (Macrophage Stimulating 1) were regulated by SNP rs3197999 (p = 5.96E-10, FDR<5%), an accepted GWAS locus for IBD. Filling the knowledge gap of molecular mechanisms between GWAS hits and disease susceptibility requires systematically dissecting the impact of the locus at the cell, mRNA expression, and protein levels. The technology and analysis tools that are now available for large-scale molecular studies can elucidate how alterations in the proteome driven by genetic polymorphisms cause or provide protection against disease. Herein, we demonstrated this directly by integrating proteomic and pQTLs with existing GWAS, mRNA expression, and eQTL datasets to provide insights into the biological processes underlying IBD and pinpoint causal genetic variants along with their downstream molecular consequences.</description><subject>Adult</subject><subject>Aging</subject><subject>Aging (Biology)</subject><subject>Aging - blood</subject><subject>Analysis</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers - blood</subject><subject>Case-Control Studies</subject><subject>Crohn's disease</subject><subject>Crohns disease</subject><subject>Disease susceptibility</subject><subject>Female</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype & phenotype</subject><subject>Health aspects</subject><subject>Hepatocyte Growth Factor - blood</subject><subject>High-Throughput Screening Assays</subject><subject>Humans</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory bowel diseases</subject><subject>Inflammatory Bowel Diseases - blood</subject><subject>Inflammatory Bowel Diseases - epidemiology</subject><subject>Inflammatory Bowel Diseases - genetics</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Proteome - genetics</subject><subject>Proteome - metabolism</subject><subject>Proteomics</subject><subject>Proto-Oncogene Proteins - blood</subject><subject>Quantitative Trait Loci</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqVk01v1DAQhiMEomXhHyCwhITgsIsd23FyQdoW2q5U0aotXC3HmSSusvFiO3z9epx2WzWohyIfYo2feTN-x5MkLwleECrIh0s7uF51i00D_YJgnPGMP0p2Ced0Lhhmj-_sd5Jn3l9iTHleiKfJTpqTtKC82E3CkWna-UXr7NC0myGg_VY5pQM480cFY3tka7TXWVuhc3DDGp06G8CujfbjyWrvEzqNHPTBo58mtOgM_AZ0QMGiZWP6Bqm-QofQQzAaHURl6_zz5EmtOg8vtt9Z8vXg88X-0fz45HC1vzyea8GLMC9FVumSllVWAlc8T3MMjOZa0VKXKSOgqhQzngpdixwqLDBNBa7zMUswltFZ8vpad9NZL7eGeUnyrOCjBTwSq2uisupSbpxZK_dbWmXkVcC6RioXK-9AiqqkJK0zVuSUMUaULiGvqC5UxXEag7Pk4_ZvQ7mGSkdPnOomotOT3rSysT9kvAEhYhR4txVw9vsAPsi18Rq6TvVgh7FukebRAEIegGapyNLiCn3zD3q_EVuqUfGupq9tLFGPonLJChr7QamI1OIeKq4K4ouwPdQmxicJ7ycJkQnwKzRq8F6uzs_-g_3ycPbk25R9e4dtQXWh9bYbxtftpyC7BrWz3juob3tHsBxn7sY5Oc6c3M5cTHt1t--3STdDRv8CeYIlYg</recordid><startdate>20170127</startdate><enddate>20170127</enddate><creator>Di Narzo, Antonio F</creator><creator>Telesco, Shannon E</creator><creator>Brodmerkel, Carrie</creator><creator>Argmann, Carmen</creator><creator>Peters, Lauren A</creator><creator>Li, Katherine</creator><creator>Kidd, Brian</creator><creator>Dudley, Joel</creator><creator>Cho, Judy</creator><creator>Schadt, Eric E</creator><creator>Kasarskis, Andrew</creator><creator>Dobrin, Radu</creator><creator>Hao, Ke</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2110-1145</orcidid><orcidid>https://orcid.org/0000-0002-1578-5029</orcidid><orcidid>https://orcid.org/0000-0002-3336-0091</orcidid><orcidid>https://orcid.org/0000-0002-3747-0474</orcidid><orcidid>https://orcid.org/0000-0002-4033-5038</orcidid></search><sort><creationdate>20170127</creationdate><title>High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors</title><author>Di Narzo, Antonio F ; Telesco, Shannon E ; Brodmerkel, Carrie ; Argmann, Carmen ; Peters, Lauren A ; Li, Katherine ; Kidd, Brian ; Dudley, Joel ; Cho, Judy ; Schadt, Eric E ; Kasarskis, Andrew ; Dobrin, Radu ; Hao, Ke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c759t-b76dcb3bd6be5a58280e438ca3bcb241ead204527cf78ed0703270f86dcb74463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aging</topic><topic>Aging (Biology)</topic><topic>Aging - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di Narzo, Antonio F</au><au>Telesco, Shannon E</au><au>Brodmerkel, Carrie</au><au>Argmann, Carmen</au><au>Peters, Lauren A</au><au>Li, Katherine</au><au>Kidd, Brian</au><au>Dudley, Joel</au><au>Cho, Judy</au><au>Schadt, Eric E</au><au>Kasarskis, Andrew</au><au>Dobrin, Radu</au><au>Hao, Ke</au><au>Barsh, Gregory S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2017-01-27</date><risdate>2017</risdate><volume>13</volume><issue>1</issue><spage>e1006565</spage><epage>e1006565</epage><pages>e1006565-e1006565</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>To date, no large scale, systematic description of the blood serum proteome has been performed in inflammatory bowel disease (IBD) patients. By using microarray technology, a more complete description of the blood proteome of IBD patients is feasible. It may help to achieve a better understanding of the disease. We analyzed blood serum profiles of 1128 proteins in IBD patients of European descent (84 Crohn's Disease (CD) subjects and 88 Ulcerative Colitis (UC) subjects) as well as 15 healthy control subjects, and linked protein variability to patient age (all cohorts) and genetic components (genotype data generated from CD patients). We discovered new, previously unreported aging-associated proteomic traits (such as serum Albumin level), confirmed previously reported results from different tissues (i.e., upregulation of APOE with aging), and found loss of regulation of MMP7 in CD patients. In carrying out a genome wide genotype-protein association study (proteomic Quantitative Trait Loci, pQTL) within the CD patients, we identified 41 distinct proteomic traits influenced by cis pQTLs (underlying SNPs are referred to as pSNPs). Significant overlaps between pQTLs and cis eQTLs corresponding to the same gene were observed and in some cases the QTL were related to inflammatory disease susceptibility. Importantly, we discovered that serum protein levels of MST1 (Macrophage Stimulating 1) were regulated by SNP rs3197999 (p = 5.96E-10, FDR<5%), an accepted GWAS locus for IBD. Filling the knowledge gap of molecular mechanisms between GWAS hits and disease susceptibility requires systematically dissecting the impact of the locus at the cell, mRNA expression, and protein levels. The technology and analysis tools that are now available for large-scale molecular studies can elucidate how alterations in the proteome driven by genetic polymorphisms cause or provide protection against disease. Herein, we demonstrated this directly by integrating proteomic and pQTLs with existing GWAS, mRNA expression, and eQTL datasets to provide insights into the biological processes underlying IBD and pinpoint causal genetic variants along with their downstream molecular consequences.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28129359</pmid><doi>10.1371/journal.pgen.1006565</doi><orcidid>https://orcid.org/0000-0003-2110-1145</orcidid><orcidid>https://orcid.org/0000-0002-1578-5029</orcidid><orcidid>https://orcid.org/0000-0002-3336-0091</orcidid><orcidid>https://orcid.org/0000-0002-3747-0474</orcidid><orcidid>https://orcid.org/0000-0002-4033-5038</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7404 |
| ispartof | PLoS genetics, 2017-01, Vol.13 (1), p.e1006565-e1006565 |
| issn | 1553-7404 1553-7390 1553-7404 |
| language | eng |
| recordid | cdi_plos_journals_1869528125 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central |
| subjects | Adult Aging Aging (Biology) Aging - blood Analysis Biology Biology and Life Sciences Biomarkers - blood Case-Control Studies Crohn's disease Crohns disease Disease susceptibility Female Genes Genetic aspects Genetic polymorphisms Genetic Predisposition to Disease Genetics Genomes Genomics Genotype & phenotype Health aspects Hepatocyte Growth Factor - blood High-Throughput Screening Assays Humans Inflammatory bowel disease Inflammatory bowel diseases Inflammatory Bowel Diseases - blood Inflammatory Bowel Diseases - epidemiology Inflammatory Bowel Diseases - genetics Male Medicine Medicine and Health Sciences Middle Aged Polymorphism, Single Nucleotide Protein expression Proteins Proteome - genetics Proteome - metabolism Proteomics Proto-Oncogene Proteins - blood Quantitative Trait Loci |
| title | High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T18%3A03%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High-Throughput%20Characterization%20of%20Blood%20Serum%20Proteomics%20of%20IBD%20Patients%20with%20Respect%20to%20Aging%20and%20Genetic%20Factors&rft.jtitle=PLoS%20genetics&rft.au=Di%20Narzo,%20Antonio%20F&rft.date=2017-01-27&rft.volume=13&rft.issue=1&rft.spage=e1006565&rft.epage=e1006565&rft.pages=e1006565-e1006565&rft.issn=1553-7404&rft.eissn=1553-7404&rft_id=info:doi/10.1371/journal.pgen.1006565&rft_dat=%3Cgale_plos_%3EA493759337%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1869528125&rft_id=info:pmid/28129359&rft_galeid=A493759337&rft_doaj_id=oai_doaj_org_article_7db312f649834441acbe8d3c9ad50298&rfr_iscdi=true |