Identification of new SLE-associated genes with a two-step Bayesian study design
In our earlier study, we utilized a Bayesian design to probe the association of ∼1000 genes (∼10 000 single-nucleotide polymorphisms (SNPs)) with systemic lupus erythematosus (SLE) on a moderate number of trios of parents and children with SLE. Two genes associated with SLE, with a multitest-correct...
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| Veröffentlicht in: | Genes and immunity 2009-07, Vol.10 (5), p.446-456 |
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| creator | Armstrong, D L Reiff, A Myones, B L Quismorio, F P Klein-Gitelman, M McCurdy, D Wagner-Weiner, L Silverman, E Ojwang, J O Kaufman, K M Kelly, J A Merrill, J T Harley, J B Bae, S-C Vyse, T J Gilkeson, G S Gaffney, P M Moser, K L Putterman, C Edberg, J C Brown, E E Ziegler, J Langefeld, C D Zidovetzki, R Jacob, C O |
| description | In our earlier study, we utilized a Bayesian design to probe the association of ∼1000 genes (∼10 000 single-nucleotide polymorphisms (SNPs)) with systemic lupus erythematosus (SLE) on a moderate number of trios of parents and children with SLE. Two genes associated with SLE, with a multitest-corrected false discovery rate (FDR) of |
| doi_str_mv | 10.1038/gene.2009.38 |
| format | Article |
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Two genes associated with SLE, with a multitest-corrected false discovery rate (FDR) of <0.05, were identified, and a number of noteworthy genes with FDR of <0.8 were also found, pointing out a future direction for the study. In this report, using a large population of controls and adult- or childhood-onset SLE cases, we have extended the earlier investigation to explore the SLE association of 10 of these noteworthy genes (109 SNPs). We have found that seven of these genes exhibit a significant (FDR<0.05) association with SLE, both confirming some genes that have earlier been found to be associated with SLE (PTPN22 and IRF5) and presenting novel findings of genes (KLRG1, interleukin-16, protein tyrosine phosphatase receptor type T, toll-like receptor (TLR)8 and CASP10), which have not been reported earlier. The results signify that the two-step candidate pathway design is an efficient way to study the genetic foundations of complex diseases. Furthermore, the novel genes identified in this study point to new directions in both the diagnosis and the eventual treatment of this debilitating disease.</description><identifier>ISSN: 1466-4879</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/gene.2009.38</identifier><identifier>PMID: 19440200</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Age of Onset ; Bayes Theorem ; Bayesian analysis ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Case-Control Studies ; Children ; Diagnosis ; Disease ; Gene Expression ; Genes ; Genetic aspects ; Genetic Predisposition to Disease ; Genetic screening ; Genome-Wide Association Study ; Genomes ; Hospitals ; Human Genetics ; Humans ; Hypotheses ; Immunity ; Immunology ; Interleukin 16 ; KLRG1 protein ; Lupus ; Lupus Erythematosus, Systemic - epidemiology ; Lupus Erythematosus, Systemic - genetics ; Medicine ; Neurosciences ; original-article ; Polymorphism, Single Nucleotide ; Probes ; Protein-tyrosine-phosphatase ; Rheumatology ; Risk factors ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Systemic lupus erythematosus ; Toll-like receptors</subject><ispartof>Genes and immunity, 2009-07, Vol.10 (5), p.446-456</ispartof><rights>Macmillan Publishers Limited 2009</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 2009</rights><rights>Macmillan Publishers Limited 2009.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c607t-482dae097d41407433a51e9eab5c1cf345655708adb9a004a811584df7cf916e3</citedby><cites>FETCH-LOGICAL-c607t-482dae097d41407433a51e9eab5c1cf345655708adb9a004a811584df7cf916e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/gene.2009.38$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/gene.2009.38$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19440200$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Armstrong, D L</creatorcontrib><creatorcontrib>Reiff, A</creatorcontrib><creatorcontrib>Myones, B L</creatorcontrib><creatorcontrib>Quismorio, F P</creatorcontrib><creatorcontrib>Klein-Gitelman, M</creatorcontrib><creatorcontrib>McCurdy, D</creatorcontrib><creatorcontrib>Wagner-Weiner, L</creatorcontrib><creatorcontrib>Silverman, E</creatorcontrib><creatorcontrib>Ojwang, J O</creatorcontrib><creatorcontrib>Kaufman, K M</creatorcontrib><creatorcontrib>Kelly, J A</creatorcontrib><creatorcontrib>Merrill, J T</creatorcontrib><creatorcontrib>Harley, J B</creatorcontrib><creatorcontrib>Bae, S-C</creatorcontrib><creatorcontrib>Vyse, T J</creatorcontrib><creatorcontrib>Gilkeson, G S</creatorcontrib><creatorcontrib>Gaffney, P M</creatorcontrib><creatorcontrib>Moser, K L</creatorcontrib><creatorcontrib>Putterman, C</creatorcontrib><creatorcontrib>Edberg, J C</creatorcontrib><creatorcontrib>Brown, E E</creatorcontrib><creatorcontrib>Ziegler, J</creatorcontrib><creatorcontrib>Langefeld, C D</creatorcontrib><creatorcontrib>Zidovetzki, R</creatorcontrib><creatorcontrib>Jacob, C O</creatorcontrib><title>Identification of new SLE-associated genes with a two-step Bayesian study design</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><addtitle>Genes Immun</addtitle><description>In our earlier study, we utilized a Bayesian design to probe the association of ∼1000 genes (∼10 000 single-nucleotide polymorphisms (SNPs)) with systemic lupus erythematosus (SLE) on a moderate number of trios of parents and children with SLE. Two genes associated with SLE, with a multitest-corrected false discovery rate (FDR) of <0.05, were identified, and a number of noteworthy genes with FDR of <0.8 were also found, pointing out a future direction for the study. In this report, using a large population of controls and adult- or childhood-onset SLE cases, we have extended the earlier investigation to explore the SLE association of 10 of these noteworthy genes (109 SNPs). We have found that seven of these genes exhibit a significant (FDR<0.05) association with SLE, both confirming some genes that have earlier been found to be associated with SLE (PTPN22 and IRF5) and presenting novel findings of genes (KLRG1, interleukin-16, protein tyrosine phosphatase receptor type T, toll-like receptor (TLR)8 and CASP10), which have not been reported earlier. The results signify that the two-step candidate pathway design is an efficient way to study the genetic foundations of complex diseases. Furthermore, the novel genes identified in this study point to new directions in both the diagnosis and the eventual treatment of this debilitating disease.</description><subject>Age of Onset</subject><subject>Bayes Theorem</subject><subject>Bayesian analysis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Case-Control Studies</subject><subject>Children</subject><subject>Diagnosis</subject><subject>Disease</subject><subject>Gene Expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic screening</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Hospitals</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Immunity</subject><subject>Immunology</subject><subject>Interleukin 16</subject><subject>KLRG1 protein</subject><subject>Lupus</subject><subject>Lupus Erythematosus, Systemic - epidemiology</subject><subject>Lupus Erythematosus, Systemic - genetics</subject><subject>Medicine</subject><subject>Neurosciences</subject><subject>original-article</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Probes</subject><subject>Protein-tyrosine-phosphatase</subject><subject>Rheumatology</subject><subject>Risk factors</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Systemic lupus erythematosus</subject><subject>Toll-like receptors</subject><issn>1466-4879</issn><issn>1476-5470</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkl2LEzEUhgdR3HX1zmsZFATBqcnk-0ZYl1ULBcXV65BmzsxmmSbdScbaf2_GFmtlRXKRr-e8J-_JKYqnGM0wIvJNBx5mNUJqRuS94hRTwStGBbo_rTmvqBTqpHgU4w1CmGOuHhYnWFGKcsxp8XnegE-uddYkF3wZ2tLDprxaXFYmxmCdSdCUU45Ybly6Lk2ZNqGKCdblO7OF6IwvYxqbbdnkTecfFw9a00d4sp_Pim_vL79efKwWnz7ML84XleVIpPyqujGAlGgopkhQQgzDoMAsmcW2JZRxxgSSplkqgxA1EmMmadMK2yrMgZwVb3e663G5gsZmF4Pp9XpwKzNsdTBOH994d6278F0TSqiUNAu83AsM4XaEmPTKRQt9bzyEMWouGFJI4f-CNVKE4V-KL_4Cb8I4-FwFXXOKBVEKTdTzf1JYZm-yVgepzvSgnW9D9mCnvPq8RqzmkvE6U7M7qDwaWDkbPLQunx8FvDoKyEyCH6kzY4x6fvXlmH29Y-0QYhyg_V1bjPTUeXrqCj11niYy48_-_I8DvG-1DFQ7IOYr38Fw8H2n4E93J9_L</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>Armstrong, D L</creator><creator>Reiff, A</creator><creator>Myones, B L</creator><creator>Quismorio, F P</creator><creator>Klein-Gitelman, M</creator><creator>McCurdy, D</creator><creator>Wagner-Weiner, L</creator><creator>Silverman, E</creator><creator>Ojwang, J O</creator><creator>Kaufman, K M</creator><creator>Kelly, J A</creator><creator>Merrill, J T</creator><creator>Harley, J B</creator><creator>Bae, S-C</creator><creator>Vyse, T J</creator><creator>Gilkeson, G S</creator><creator>Gaffney, P M</creator><creator>Moser, K L</creator><creator>Putterman, C</creator><creator>Edberg, J C</creator><creator>Brown, E E</creator><creator>Ziegler, J</creator><creator>Langefeld, C D</creator><creator>Zidovetzki, R</creator><creator>Jacob, C O</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>ISR</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</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>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090701</creationdate><title>Identification of new SLE-associated genes with a two-step Bayesian study design</title><author>Armstrong, D L ; Reiff, A ; Myones, B L ; Quismorio, F P ; Klein-Gitelman, M ; McCurdy, D ; Wagner-Weiner, L ; Silverman, E ; Ojwang, J O ; Kaufman, K M ; Kelly, J A ; Merrill, J T ; Harley, J B ; Bae, S-C ; Vyse, T J ; Gilkeson, G S ; Gaffney, P M ; Moser, K L ; Putterman, C ; Edberg, J C ; Brown, E E ; Ziegler, J ; Langefeld, C D ; Zidovetzki, R ; Jacob, C O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c607t-482dae097d41407433a51e9eab5c1cf345655708adb9a004a811584df7cf916e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Age of Onset</topic><topic>Bayes Theorem</topic><topic>Bayesian analysis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Case-Control Studies</topic><topic>Children</topic><topic>Diagnosis</topic><topic>Disease</topic><topic>Gene Expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic screening</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Hospitals</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Immunity</topic><topic>Immunology</topic><topic>Interleukin 16</topic><topic>KLRG1 protein</topic><topic>Lupus</topic><topic>Lupus Erythematosus, Systemic - epidemiology</topic><topic>Lupus Erythematosus, Systemic - genetics</topic><topic>Medicine</topic><topic>Neurosciences</topic><topic>original-article</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Probes</topic><topic>Protein-tyrosine-phosphatase</topic><topic>Rheumatology</topic><topic>Risk factors</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Systemic lupus erythematosus</topic><topic>Toll-like receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Armstrong, D L</creatorcontrib><creatorcontrib>Reiff, A</creatorcontrib><creatorcontrib>Myones, B L</creatorcontrib><creatorcontrib>Quismorio, F P</creatorcontrib><creatorcontrib>Klein-Gitelman, M</creatorcontrib><creatorcontrib>McCurdy, D</creatorcontrib><creatorcontrib>Wagner-Weiner, L</creatorcontrib><creatorcontrib>Silverman, E</creatorcontrib><creatorcontrib>Ojwang, J O</creatorcontrib><creatorcontrib>Kaufman, K M</creatorcontrib><creatorcontrib>Kelly, J A</creatorcontrib><creatorcontrib>Merrill, J T</creatorcontrib><creatorcontrib>Harley, J B</creatorcontrib><creatorcontrib>Bae, S-C</creatorcontrib><creatorcontrib>Vyse, T J</creatorcontrib><creatorcontrib>Gilkeson, G S</creatorcontrib><creatorcontrib>Gaffney, P M</creatorcontrib><creatorcontrib>Moser, K L</creatorcontrib><creatorcontrib>Putterman, C</creatorcontrib><creatorcontrib>Edberg, J C</creatorcontrib><creatorcontrib>Brown, E E</creatorcontrib><creatorcontrib>Ziegler, J</creatorcontrib><creatorcontrib>Langefeld, C D</creatorcontrib><creatorcontrib>Zidovetzki, R</creatorcontrib><creatorcontrib>Jacob, C O</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Armstrong, D L</au><au>Reiff, A</au><au>Myones, B L</au><au>Quismorio, F P</au><au>Klein-Gitelman, M</au><au>McCurdy, D</au><au>Wagner-Weiner, L</au><au>Silverman, E</au><au>Ojwang, J O</au><au>Kaufman, K M</au><au>Kelly, J A</au><au>Merrill, J T</au><au>Harley, J B</au><au>Bae, S-C</au><au>Vyse, T J</au><au>Gilkeson, G S</au><au>Gaffney, P M</au><au>Moser, K L</au><au>Putterman, C</au><au>Edberg, J C</au><au>Brown, E E</au><au>Ziegler, J</au><au>Langefeld, C D</au><au>Zidovetzki, R</au><au>Jacob, C O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of new SLE-associated genes with a two-step Bayesian study design</atitle><jtitle>Genes and immunity</jtitle><stitle>Genes Immun</stitle><addtitle>Genes Immun</addtitle><date>2009-07-01</date><risdate>2009</risdate><volume>10</volume><issue>5</issue><spage>446</spage><epage>456</epage><pages>446-456</pages><issn>1466-4879</issn><eissn>1476-5470</eissn><abstract>In our earlier study, we utilized a Bayesian design to probe the association of ∼1000 genes (∼10 000 single-nucleotide polymorphisms (SNPs)) with systemic lupus erythematosus (SLE) on a moderate number of trios of parents and children with SLE. Two genes associated with SLE, with a multitest-corrected false discovery rate (FDR) of <0.05, were identified, and a number of noteworthy genes with FDR of <0.8 were also found, pointing out a future direction for the study. In this report, using a large population of controls and adult- or childhood-onset SLE cases, we have extended the earlier investigation to explore the SLE association of 10 of these noteworthy genes (109 SNPs). We have found that seven of these genes exhibit a significant (FDR<0.05) association with SLE, both confirming some genes that have earlier been found to be associated with SLE (PTPN22 and IRF5) and presenting novel findings of genes (KLRG1, interleukin-16, protein tyrosine phosphatase receptor type T, toll-like receptor (TLR)8 and CASP10), which have not been reported earlier. The results signify that the two-step candidate pathway design is an efficient way to study the genetic foundations of complex diseases. Furthermore, the novel genes identified in this study point to new directions in both the diagnosis and the eventual treatment of this debilitating disease.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19440200</pmid><doi>10.1038/gene.2009.38</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Age of Onset Bayes Theorem Bayesian analysis Biomedical and Life Sciences Biomedicine Cancer Research Case-Control Studies Children Diagnosis Disease Gene Expression Genes Genetic aspects Genetic Predisposition to Disease Genetic screening Genome-Wide Association Study Genomes Hospitals Human Genetics Humans Hypotheses Immunity Immunology Interleukin 16 KLRG1 protein Lupus Lupus Erythematosus, Systemic - epidemiology Lupus Erythematosus, Systemic - genetics Medicine Neurosciences original-article Polymorphism, Single Nucleotide Probes Protein-tyrosine-phosphatase Rheumatology Risk factors Single nucleotide polymorphisms Single-nucleotide polymorphism Systemic lupus erythematosus Toll-like receptors |
| title | Identification of new SLE-associated genes with a two-step Bayesian study design |
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