Eintrag weiter verarbeiten
eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes
Gespeichert in:
| Zeitschriftentitel: | Allergy |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , |
| In: | Allergy, 70, 2015, 10, S. 1309-1318 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Li, X. Hastie, A. T. Hawkins, G. A. Moore, W. C. Ampleford, E. J. Milosevic, J. Li, H. Busse, W. W. Erzurum, S. C. Kaminski, N. Wenzel, S. E. Meyers, D. A. Bleecker, E. R. Li, X. Hastie, A. T. Hawkins, G. A. Moore, W. C. Ampleford, E. J. Milosevic, J. Li, H. Busse, W. W. Erzurum, S. C. Kaminski, N. Wenzel, S. E. Meyers, D. A. Bleecker, E. R. |
|---|---|
| author |
Li, X. Hastie, A. T. Hawkins, G. A. Moore, W. C. Ampleford, E. J. Milosevic, J. Li, H. Busse, W. W. Erzurum, S. C. Kaminski, N. Wenzel, S. E. Meyers, D. A. Bleecker, E. R. |
| spellingShingle |
Li, X. Hastie, A. T. Hawkins, G. A. Moore, W. C. Ampleford, E. J. Milosevic, J. Li, H. Busse, W. W. Erzurum, S. C. Kaminski, N. Wenzel, S. E. Meyers, D. A. Bleecker, E. R. Allergy eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes Immunology Immunology and Allergy |
| author_sort |
li, x. |
| spelling |
Li, X. Hastie, A. T. Hawkins, G. A. Moore, W. C. Ampleford, E. J. Milosevic, J. Li, H. Busse, W. W. Erzurum, S. C. Kaminski, N. Wenzel, S. E. Meyers, D. A. Bleecker, E. R. 0105-4538 1398-9995 Wiley Immunology Immunology and Allergy http://dx.doi.org/10.1111/all.12683 <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Genome‐wide association studies (<jats:styled-content style="fixed-case">GWAS</jats:styled-content>s) have identified various genes associated with asthma, yet, causal genes or single nucleotide polymorphisms (<jats:styled-content style="fixed-case">SNP</jats:styled-content>s) remain elusive. We sought to dissect functional genes/<jats:styled-content style="fixed-case">SNP</jats:styled-content>s for asthma by combining expression quantitative trait loci (<jats:styled-content style="fixed-case">eQTL</jats:styled-content>s) and <jats:styled-content style="fixed-case">GWAS</jats:styled-content>s.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:italic>Cis</jats:italic>‐<jats:styled-content style="fixed-case">eQTL</jats:styled-content> analyses of 34 asthma genes were performed in cells from human bronchial epithelial biopsy (<jats:styled-content style="fixed-case">BEC</jats:styled-content>,<jats:italic> n</jats:italic> = 107) and from bronchial alveolar lavage (<jats:styled-content style="fixed-case">BAL</jats:styled-content>,<jats:italic> n</jats:italic> = 94).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>For <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content>‐<jats:styled-content style="fixed-case">WDR</jats:styled-content>36</jats:italic> region, rs3806932 (G allele protective against eosinophilic esophagitis) and rs2416257 (A allele associated with lower eosinophil counts and protective against asthma) were correlated with decreased expression of <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> in <jats:styled-content style="fixed-case">BAL</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>7.9 × 10<jats:sup>−11</jats:sup> and 5.4 × 10<jats:sup>−4</jats:sup>, respectively) and <jats:styled-content style="fixed-case">BEC</jats:styled-content>, but not <jats:italic><jats:styled-content style="fixed-case">WDR</jats:styled-content>36</jats:italic>. Surprisingly, rs1837253 (consistently associated with asthma) showed no correlation with <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> expression levels. For <jats:italic><jats:styled-content style="fixed-case">ORMDL</jats:styled-content>3‐<jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic> region, rs8067378 (G allele protective against asthma) was correlated with decreased expression of <jats:italic><jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic> in <jats:styled-content style="fixed-case">BEC</jats:styled-content> and <jats:styled-content style="fixed-case">BAL</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>1.3 × 10<jats:sup>−4</jats:sup> and 0.04) but not <jats:italic><jats:styled-content style="fixed-case">ORMDL</jats:styled-content>3</jats:italic>. rs992969 in the promoter region of <jats:italic><jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic> (A allele associated with higher eosinophil counts and risk for asthma) was correlated with increased expression of <jats:italic><jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic> in <jats:styled-content style="fixed-case">BEC</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>1.3 × 10<jats:sup>−6</jats:sup>) but not in <jats:styled-content style="fixed-case">BAL</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our study illustrates cell‐type‐specific regulation of the expression of asthma‐related genes documenting <jats:styled-content style="fixed-case">SNP</jats:styled-content>s in <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">HLA</jats:styled-content>‐<jats:styled-content style="fixed-case">DQB</jats:styled-content>1</jats:italic>,<jats:italic> C11orf30</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">DEXI</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">CDHR</jats:styled-content>3</jats:italic>, and <jats:italic><jats:styled-content style="fixed-case">ZBTB</jats:styled-content>10</jats:italic> affect asthma risk through <jats:italic>cis</jats:italic>‐regulation of its gene expression. Whenever possible, disease‐relevant tissues should be used for transcription analysis. <jats:styled-content style="fixed-case">SNP</jats:styled-content>s in <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> may affect asthma risk through up‐regulating <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> <jats:styled-content style="fixed-case">mRNA</jats:styled-content> expression or protein secretion. Further functional studies are warranted.</jats:p></jats:sec> <scp>eQTL</scp> of bronchial epithelial cells and bronchial alveolar lavage deciphers <scp>GWAS</scp>‐identified asthma genes Allergy |
| doi_str_mv |
10.1111/all.12683 |
| facet_avail |
Online Free |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMS9hbGwuMTI2ODM |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMS9hbGwuMTI2ODM |
| institution |
DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Rs1 DE-Pl11 DE-105 DE-14 DE-Ch1 DE-L229 |
| imprint |
Wiley, 2015 |
| imprint_str_mv |
Wiley, 2015 |
| issn |
0105-4538 1398-9995 |
| issn_str_mv |
0105-4538 1398-9995 |
| language |
English |
| mega_collection |
Wiley (CrossRef) |
| match_str |
li2015eqtlofbronchialepithelialcellsandbronchialalveolarlavagedeciphersgwasidentifiedasthmagenes |
| publishDateSort |
2015 |
| publisher |
Wiley |
| recordtype |
ai |
| record_format |
ai |
| series |
Allergy |
| source_id |
49 |
| title |
eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_unstemmed |
eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_full |
eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_fullStr |
eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_full_unstemmed |
eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_short |
eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_sort |
<scp>eqtl</scp> of bronchial epithelial cells and bronchial alveolar lavage deciphers <scp>gwas</scp>‐identified asthma genes |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.1111/all.12683 |
| publishDate |
2015 |
| physical |
1309-1318 |
| description |
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Genome‐wide association studies (<jats:styled-content style="fixed-case">GWAS</jats:styled-content>s) have identified various genes associated with asthma, yet, causal genes or single nucleotide polymorphisms (<jats:styled-content style="fixed-case">SNP</jats:styled-content>s) remain elusive. We sought to dissect functional genes/<jats:styled-content style="fixed-case">SNP</jats:styled-content>s for asthma by combining expression quantitative trait loci (<jats:styled-content style="fixed-case">eQTL</jats:styled-content>s) and <jats:styled-content style="fixed-case">GWAS</jats:styled-content>s.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:italic>Cis</jats:italic>‐<jats:styled-content style="fixed-case">eQTL</jats:styled-content> analyses of 34 asthma genes were performed in cells from human bronchial epithelial biopsy (<jats:styled-content style="fixed-case">BEC</jats:styled-content>,<jats:italic> n</jats:italic> = 107) and from bronchial alveolar lavage (<jats:styled-content style="fixed-case">BAL</jats:styled-content>,<jats:italic> n</jats:italic> = 94).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>For <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content>‐<jats:styled-content style="fixed-case">WDR</jats:styled-content>36</jats:italic> region, rs3806932 (G allele protective against eosinophilic esophagitis) and rs2416257 (A allele associated with lower eosinophil counts and protective against asthma) were correlated with decreased expression of <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> in <jats:styled-content style="fixed-case">BAL</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>7.9 × 10<jats:sup>−11</jats:sup> and 5.4 × 10<jats:sup>−4</jats:sup>, respectively) and <jats:styled-content style="fixed-case">BEC</jats:styled-content>, but not <jats:italic><jats:styled-content style="fixed-case">WDR</jats:styled-content>36</jats:italic>. Surprisingly, rs1837253 (consistently associated with asthma) showed no correlation with <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> expression levels. For <jats:italic><jats:styled-content style="fixed-case">ORMDL</jats:styled-content>3‐<jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic> region, rs8067378 (G allele protective against asthma) was correlated with decreased expression of <jats:italic><jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic> in <jats:styled-content style="fixed-case">BEC</jats:styled-content> and <jats:styled-content style="fixed-case">BAL</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>1.3 × 10<jats:sup>−4</jats:sup> and 0.04) but not <jats:italic><jats:styled-content style="fixed-case">ORMDL</jats:styled-content>3</jats:italic>. rs992969 in the promoter region of <jats:italic><jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic> (A allele associated with higher eosinophil counts and risk for asthma) was correlated with increased expression of <jats:italic><jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic> in <jats:styled-content style="fixed-case">BEC</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>1.3 × 10<jats:sup>−6</jats:sup>) but not in <jats:styled-content style="fixed-case">BAL</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our study illustrates cell‐type‐specific regulation of the expression of asthma‐related genes documenting <jats:styled-content style="fixed-case">SNP</jats:styled-content>s in <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">HLA</jats:styled-content>‐<jats:styled-content style="fixed-case">DQB</jats:styled-content>1</jats:italic>,<jats:italic> C11orf30</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">DEXI</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">CDHR</jats:styled-content>3</jats:italic>, and <jats:italic><jats:styled-content style="fixed-case">ZBTB</jats:styled-content>10</jats:italic> affect asthma risk through <jats:italic>cis</jats:italic>‐regulation of its gene expression. Whenever possible, disease‐relevant tissues should be used for transcription analysis. <jats:styled-content style="fixed-case">SNP</jats:styled-content>s in <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> may affect asthma risk through up‐regulating <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> <jats:styled-content style="fixed-case">mRNA</jats:styled-content> expression or protein secretion. Further functional studies are warranted.</jats:p></jats:sec> |
| container_issue |
10 |
| container_start_page |
1309 |
| container_title |
Allergy |
| container_volume |
70 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792338279375306752 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T15:29:10.351Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=eQTL+of+bronchial+epithelial+cells+and+bronchial+alveolar+lavage+deciphers+GWAS%E2%80%90identified+asthma+genes&rft.date=2015-10-01&genre=article&issn=1398-9995&volume=70&issue=10&spage=1309&epage=1318&pages=1309-1318&jtitle=Allergy&atitle=%3Cscp%3EeQTL%3C%2Fscp%3E+of+bronchial+epithelial+cells+and+bronchial+alveolar+lavage+deciphers+%3Cscp%3EGWAS%3C%2Fscp%3E%E2%80%90identified+asthma+genes&aulast=Bleecker&aufirst=E.+R.&rft_id=info%3Adoi%2F10.1111%2Fall.12683&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792338279375306752 |
| author | Li, X., Hastie, A. T., Hawkins, G. A., Moore, W. C., Ampleford, E. J., Milosevic, J., Li, H., Busse, W. W., Erzurum, S. C., Kaminski, N., Wenzel, S. E., Meyers, D. A., Bleecker, E. R. |
| author_facet | Li, X., Hastie, A. T., Hawkins, G. A., Moore, W. C., Ampleford, E. J., Milosevic, J., Li, H., Busse, W. W., Erzurum, S. C., Kaminski, N., Wenzel, S. E., Meyers, D. A., Bleecker, E. R., Li, X., Hastie, A. T., Hawkins, G. A., Moore, W. C., Ampleford, E. J., Milosevic, J., Li, H., Busse, W. W., Erzurum, S. C., Kaminski, N., Wenzel, S. E., Meyers, D. A., Bleecker, E. R. |
| author_sort | li, x. |
| container_issue | 10 |
| container_start_page | 1309 |
| container_title | Allergy |
| container_volume | 70 |
| description | <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Genome‐wide association studies (<jats:styled-content style="fixed-case">GWAS</jats:styled-content>s) have identified various genes associated with asthma, yet, causal genes or single nucleotide polymorphisms (<jats:styled-content style="fixed-case">SNP</jats:styled-content>s) remain elusive. We sought to dissect functional genes/<jats:styled-content style="fixed-case">SNP</jats:styled-content>s for asthma by combining expression quantitative trait loci (<jats:styled-content style="fixed-case">eQTL</jats:styled-content>s) and <jats:styled-content style="fixed-case">GWAS</jats:styled-content>s.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:italic>Cis</jats:italic>‐<jats:styled-content style="fixed-case">eQTL</jats:styled-content> analyses of 34 asthma genes were performed in cells from human bronchial epithelial biopsy (<jats:styled-content style="fixed-case">BEC</jats:styled-content>,<jats:italic> n</jats:italic> = 107) and from bronchial alveolar lavage (<jats:styled-content style="fixed-case">BAL</jats:styled-content>,<jats:italic> n</jats:italic> = 94).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>For <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content>‐<jats:styled-content style="fixed-case">WDR</jats:styled-content>36</jats:italic> region, rs3806932 (G allele protective against eosinophilic esophagitis) and rs2416257 (A allele associated with lower eosinophil counts and protective against asthma) were correlated with decreased expression of <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> in <jats:styled-content style="fixed-case">BAL</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>7.9 × 10<jats:sup>−11</jats:sup> and 5.4 × 10<jats:sup>−4</jats:sup>, respectively) and <jats:styled-content style="fixed-case">BEC</jats:styled-content>, but not <jats:italic><jats:styled-content style="fixed-case">WDR</jats:styled-content>36</jats:italic>. Surprisingly, rs1837253 (consistently associated with asthma) showed no correlation with <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> expression levels. For <jats:italic><jats:styled-content style="fixed-case">ORMDL</jats:styled-content>3‐<jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic> region, rs8067378 (G allele protective against asthma) was correlated with decreased expression of <jats:italic><jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic> in <jats:styled-content style="fixed-case">BEC</jats:styled-content> and <jats:styled-content style="fixed-case">BAL</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>1.3 × 10<jats:sup>−4</jats:sup> and 0.04) but not <jats:italic><jats:styled-content style="fixed-case">ORMDL</jats:styled-content>3</jats:italic>. rs992969 in the promoter region of <jats:italic><jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic> (A allele associated with higher eosinophil counts and risk for asthma) was correlated with increased expression of <jats:italic><jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic> in <jats:styled-content style="fixed-case">BEC</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>1.3 × 10<jats:sup>−6</jats:sup>) but not in <jats:styled-content style="fixed-case">BAL</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our study illustrates cell‐type‐specific regulation of the expression of asthma‐related genes documenting <jats:styled-content style="fixed-case">SNP</jats:styled-content>s in <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">HLA</jats:styled-content>‐<jats:styled-content style="fixed-case">DQB</jats:styled-content>1</jats:italic>,<jats:italic> C11orf30</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">DEXI</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">CDHR</jats:styled-content>3</jats:italic>, and <jats:italic><jats:styled-content style="fixed-case">ZBTB</jats:styled-content>10</jats:italic> affect asthma risk through <jats:italic>cis</jats:italic>‐regulation of its gene expression. Whenever possible, disease‐relevant tissues should be used for transcription analysis. <jats:styled-content style="fixed-case">SNP</jats:styled-content>s in <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> may affect asthma risk through up‐regulating <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> <jats:styled-content style="fixed-case">mRNA</jats:styled-content> expression or protein secretion. Further functional studies are warranted.</jats:p></jats:sec> |
| doi_str_mv | 10.1111/all.12683 |
| facet_avail | Online, Free |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMS9hbGwuMTI2ODM |
| imprint | Wiley, 2015 |
| imprint_str_mv | Wiley, 2015 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Rs1, DE-Pl11, DE-105, DE-14, DE-Ch1, DE-L229 |
| issn | 0105-4538, 1398-9995 |
| issn_str_mv | 0105-4538, 1398-9995 |
| language | English |
| last_indexed | 2024-03-01T15:29:10.351Z |
| match_str | li2015eqtlofbronchialepithelialcellsandbronchialalveolarlavagedeciphersgwasidentifiedasthmagenes |
| mega_collection | Wiley (CrossRef) |
| physical | 1309-1318 |
| publishDate | 2015 |
| publishDateSort | 2015 |
| publisher | Wiley |
| record_format | ai |
| recordtype | ai |
| series | Allergy |
| source_id | 49 |
| spelling | Li, X. Hastie, A. T. Hawkins, G. A. Moore, W. C. Ampleford, E. J. Milosevic, J. Li, H. Busse, W. W. Erzurum, S. C. Kaminski, N. Wenzel, S. E. Meyers, D. A. Bleecker, E. R. 0105-4538 1398-9995 Wiley Immunology Immunology and Allergy http://dx.doi.org/10.1111/all.12683 <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Genome‐wide association studies (<jats:styled-content style="fixed-case">GWAS</jats:styled-content>s) have identified various genes associated with asthma, yet, causal genes or single nucleotide polymorphisms (<jats:styled-content style="fixed-case">SNP</jats:styled-content>s) remain elusive. We sought to dissect functional genes/<jats:styled-content style="fixed-case">SNP</jats:styled-content>s for asthma by combining expression quantitative trait loci (<jats:styled-content style="fixed-case">eQTL</jats:styled-content>s) and <jats:styled-content style="fixed-case">GWAS</jats:styled-content>s.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:italic>Cis</jats:italic>‐<jats:styled-content style="fixed-case">eQTL</jats:styled-content> analyses of 34 asthma genes were performed in cells from human bronchial epithelial biopsy (<jats:styled-content style="fixed-case">BEC</jats:styled-content>,<jats:italic> n</jats:italic> = 107) and from bronchial alveolar lavage (<jats:styled-content style="fixed-case">BAL</jats:styled-content>,<jats:italic> n</jats:italic> = 94).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>For <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content>‐<jats:styled-content style="fixed-case">WDR</jats:styled-content>36</jats:italic> region, rs3806932 (G allele protective against eosinophilic esophagitis) and rs2416257 (A allele associated with lower eosinophil counts and protective against asthma) were correlated with decreased expression of <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> in <jats:styled-content style="fixed-case">BAL</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>7.9 × 10<jats:sup>−11</jats:sup> and 5.4 × 10<jats:sup>−4</jats:sup>, respectively) and <jats:styled-content style="fixed-case">BEC</jats:styled-content>, but not <jats:italic><jats:styled-content style="fixed-case">WDR</jats:styled-content>36</jats:italic>. Surprisingly, rs1837253 (consistently associated with asthma) showed no correlation with <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> expression levels. For <jats:italic><jats:styled-content style="fixed-case">ORMDL</jats:styled-content>3‐<jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic> region, rs8067378 (G allele protective against asthma) was correlated with decreased expression of <jats:italic><jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic> in <jats:styled-content style="fixed-case">BEC</jats:styled-content> and <jats:styled-content style="fixed-case">BAL</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>1.3 × 10<jats:sup>−4</jats:sup> and 0.04) but not <jats:italic><jats:styled-content style="fixed-case">ORMDL</jats:styled-content>3</jats:italic>. rs992969 in the promoter region of <jats:italic><jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic> (A allele associated with higher eosinophil counts and risk for asthma) was correlated with increased expression of <jats:italic><jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic> in <jats:styled-content style="fixed-case">BEC</jats:styled-content> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>1.3 × 10<jats:sup>−6</jats:sup>) but not in <jats:styled-content style="fixed-case">BAL</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our study illustrates cell‐type‐specific regulation of the expression of asthma‐related genes documenting <jats:styled-content style="fixed-case">SNP</jats:styled-content>s in <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">GSDMB</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">IL</jats:styled-content>33</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">HLA</jats:styled-content>‐<jats:styled-content style="fixed-case">DQB</jats:styled-content>1</jats:italic>,<jats:italic> C11orf30</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">DEXI</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">CDHR</jats:styled-content>3</jats:italic>, and <jats:italic><jats:styled-content style="fixed-case">ZBTB</jats:styled-content>10</jats:italic> affect asthma risk through <jats:italic>cis</jats:italic>‐regulation of its gene expression. Whenever possible, disease‐relevant tissues should be used for transcription analysis. <jats:styled-content style="fixed-case">SNP</jats:styled-content>s in <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> may affect asthma risk through up‐regulating <jats:italic><jats:styled-content style="fixed-case">TSLP</jats:styled-content></jats:italic> <jats:styled-content style="fixed-case">mRNA</jats:styled-content> expression or protein secretion. Further functional studies are warranted.</jats:p></jats:sec> <scp>eQTL</scp> of bronchial epithelial cells and bronchial alveolar lavage deciphers <scp>GWAS</scp>‐identified asthma genes Allergy |
| spellingShingle | Li, X., Hastie, A. T., Hawkins, G. A., Moore, W. C., Ampleford, E. J., Milosevic, J., Li, H., Busse, W. W., Erzurum, S. C., Kaminski, N., Wenzel, S. E., Meyers, D. A., Bleecker, E. R., Allergy, eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes, Immunology, Immunology and Allergy |
| title | eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_full | eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_fullStr | eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_full_unstemmed | eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_short | eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| title_sort | <scp>eqtl</scp> of bronchial epithelial cells and bronchial alveolar lavage deciphers <scp>gwas</scp>‐identified asthma genes |
| title_unstemmed | eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.1111/all.12683 |