Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children
Objectives We aimed to investigate the role of genetics in the respiratory response of asthmatic children to air pollution, with a genome-wide level analysis of gene by nitrogen dioxide (NO 2 ) and carbon monoxide (CO) interaction on lung function and to identify biological pathways involved. Method...
Gespeichert in:
| Veröffentlicht in: | Journal of exposure science & environmental epidemiology 2019-06, Vol.29 (4), p.539-547 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 547 |
|---|---|
| container_issue | 4 |
| container_start_page | 539 |
| container_title | Journal of exposure science & environmental epidemiology |
| container_volume | 29 |
| creator | Ierodiakonou, Despo Coull, Brent A. Zanobetti, Antonella Postma, Dirkje S. Boezen, H. Marike Vonk, Judith M. McKone, Edward F. Schildcrout, Jonathan S. Koppelman, Gerard H. Croteau-Chonka, Damien C. Lumley, Thomas Koutrakis, Petros Schwartz, Joel Gold, Diane R. Weiss, Scott T. |
| description | Objectives
We aimed to investigate the role of genetics in the respiratory response of asthmatic children to air pollution, with a genome-wide level analysis of gene by nitrogen dioxide (NO
2
) and carbon monoxide (CO) interaction on lung function and to identify biological pathways involved.
Methods
We used a two-step method for fast linear mixed model computations for genome-wide association studies, exploring whether variants modify the longitudinal relationship between 4-month average pollution and post-bronchodilator FEV
1
in 522 Caucasian and 88 African-American asthmatic children. Top hits were confirmed with classic linear mixed-effect models. We used the improved gene set enrichment analysis for GWAS (
i-GSEA4GWAS
) to identify plausible pathways.
Results
Two SNPs near the
EPHA3
(rs13090972 and rs958144) and one in
TXNDC8
(rs7041938) showed significant interactions with NO
2
in Caucasians but we did not replicate this locus in African-Americans. SNP–CO interactions did not reach genome-wide significance. The
i-GSEA4GWAS
showed a pathway linked to the HO-1/CO system to be associated with CO-related FEV
1
changes. For NO
2
-related FEV
1
responses, we identified pathways involved in cellular adhesion, oxidative stress, inflammation, and metabolic responses.
Conclusion
The host lung function response to long-term exposure to pollution is linked to genes involved in cellular adhesion, oxidative stress, inflammatory, and metabolic pathways. |
| doi_str_mv | 10.1038/s41370-019-0136-3 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10730425</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A590692969</galeid><sourcerecordid>A590692969</sourcerecordid><originalsourceid>FETCH-LOGICAL-c569t-ccc38c956f7827a960cc44a24d524332b8e475aca641dd9d3c208c5d04ef3a523</originalsourceid><addsrcrecordid>eNp1kl1rFDEUhgdRbK3-AG9kQBBvpuZ7JldSil9Q0AsF78LZJLOTkknWZMay_96MU7ddUULISfKcN8nJW1XPMTrHiHZvMsO0RQ3CsnQqGvqgOsWcl5lg3x8eYopPqic5XyPEWCvQ4-qEYkQ60qHTSn2BabiBfQ0B_D67XMe-hnprQxxtc-OMXWJbbwrhUr2L3s-Ti6F2YbIJ9O84T7PZl5Ua8jSMMDld68F5k2x4Wj3qwWf77HY8q769f_f18mNz9fnDp8uLq0ZzIadGa007Lbno2460IAXSmjEgzHDCKCWbzrKWgwbBsDHSUE1Qp7lBzPYUOKFn1dtVdzdvRmu0DVMCr3bJjZD2KoJTxzvBDWobfyqMWooY4UXh9a1Cij9mmyc1uqyt9xBsnLMiBAvScSxRQV_-hV7HOZUCLhQThJRLyztqC94qF_pYDtaLqLrgEglJpFio839QpRk7Oh2D7V1ZP0p4dS9hsOCnIcf1V_IxiFdQp5hzsv2hGhipxT9q9Y8q_lGLfxQtOS_ul_GQ8ccwBSArkMtW2Np09_T_q_4CwJzPGw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2246225249</pqid></control><display><type>article</type><title>Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Ierodiakonou, Despo ; Coull, Brent A. ; Zanobetti, Antonella ; Postma, Dirkje S. ; Boezen, H. Marike ; Vonk, Judith M. ; McKone, Edward F. ; Schildcrout, Jonathan S. ; Koppelman, Gerard H. ; Croteau-Chonka, Damien C. ; Lumley, Thomas ; Koutrakis, Petros ; Schwartz, Joel ; Gold, Diane R. ; Weiss, Scott T.</creator><creatorcontrib>Ierodiakonou, Despo ; Coull, Brent A. ; Zanobetti, Antonella ; Postma, Dirkje S. ; Boezen, H. Marike ; Vonk, Judith M. ; McKone, Edward F. ; Schildcrout, Jonathan S. ; Koppelman, Gerard H. ; Croteau-Chonka, Damien C. ; Lumley, Thomas ; Koutrakis, Petros ; Schwartz, Joel ; Gold, Diane R. ; Weiss, Scott T.</creatorcontrib><description>Objectives
We aimed to investigate the role of genetics in the respiratory response of asthmatic children to air pollution, with a genome-wide level analysis of gene by nitrogen dioxide (NO
2
) and carbon monoxide (CO) interaction on lung function and to identify biological pathways involved.
Methods
We used a two-step method for fast linear mixed model computations for genome-wide association studies, exploring whether variants modify the longitudinal relationship between 4-month average pollution and post-bronchodilator FEV
1
in 522 Caucasian and 88 African-American asthmatic children. Top hits were confirmed with classic linear mixed-effect models. We used the improved gene set enrichment analysis for GWAS (
i-GSEA4GWAS
) to identify plausible pathways.
Results
Two SNPs near the
EPHA3
(rs13090972 and rs958144) and one in
TXNDC8
(rs7041938) showed significant interactions with NO
2
in Caucasians but we did not replicate this locus in African-Americans. SNP–CO interactions did not reach genome-wide significance. The
i-GSEA4GWAS
showed a pathway linked to the HO-1/CO system to be associated with CO-related FEV
1
changes. For NO
2
-related FEV
1
responses, we identified pathways involved in cellular adhesion, oxidative stress, inflammation, and metabolic responses.
Conclusion
The host lung function response to long-term exposure to pollution is linked to genes involved in cellular adhesion, oxidative stress, inflammatory, and metabolic pathways.</description><identifier>ISSN: 1559-0631</identifier><identifier>ISSN: 1559-064X</identifier><identifier>EISSN: 1559-064X</identifier><identifier>DOI: 10.1038/s41370-019-0136-3</identifier><identifier>PMID: 31028280</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adhesion ; Air Pollutants - analysis ; Air Pollutants - toxicity ; Air pollution ; Asthma ; Asthma - physiopathology ; Asthma in children ; Bronchodilators ; Carbon monoxide ; Carbon Monoxide - analysis ; Child ; Children ; Epidemiology ; Female ; Gene set enrichment analysis ; Genetic aspects ; Genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Health aspects ; Humans ; Identification methods ; Inflammation ; Lung - physiopathology ; Lungs ; Male ; Medicine ; Medicine & Public Health ; Metabolic pathways ; Metabolic response ; Metabolism ; Nitrogen dioxide ; Nitrogen Dioxide - analysis ; Oxidative stress ; Physiological aspects ; Pollution ; Respiratory function ; Respiratory Function Tests ; Single-nucleotide polymorphism</subject><ispartof>Journal of exposure science & environmental epidemiology, 2019-06, Vol.29 (4), p.539-547</ispartof><rights>Springer Nature America, Inc. 2019</rights><rights>COPYRIGHT 2019 Nature Publishing Group</rights><rights>Springer Nature America, Inc. 2019.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c569t-ccc38c956f7827a960cc44a24d524332b8e475aca641dd9d3c208c5d04ef3a523</citedby><cites>FETCH-LOGICAL-c569t-ccc38c956f7827a960cc44a24d524332b8e475aca641dd9d3c208c5d04ef3a523</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/s41370-019-0136-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41370-019-0136-3$$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/31028280$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ierodiakonou, Despo</creatorcontrib><creatorcontrib>Coull, Brent A.</creatorcontrib><creatorcontrib>Zanobetti, Antonella</creatorcontrib><creatorcontrib>Postma, Dirkje S.</creatorcontrib><creatorcontrib>Boezen, H. Marike</creatorcontrib><creatorcontrib>Vonk, Judith M.</creatorcontrib><creatorcontrib>McKone, Edward F.</creatorcontrib><creatorcontrib>Schildcrout, Jonathan S.</creatorcontrib><creatorcontrib>Koppelman, Gerard H.</creatorcontrib><creatorcontrib>Croteau-Chonka, Damien C.</creatorcontrib><creatorcontrib>Lumley, Thomas</creatorcontrib><creatorcontrib>Koutrakis, Petros</creatorcontrib><creatorcontrib>Schwartz, Joel</creatorcontrib><creatorcontrib>Gold, Diane R.</creatorcontrib><creatorcontrib>Weiss, Scott T.</creatorcontrib><title>Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children</title><title>Journal of exposure science & environmental epidemiology</title><addtitle>J Expo Sci Environ Epidemiol</addtitle><addtitle>J Expo Sci Environ Epidemiol</addtitle><description>Objectives
We aimed to investigate the role of genetics in the respiratory response of asthmatic children to air pollution, with a genome-wide level analysis of gene by nitrogen dioxide (NO
2
) and carbon monoxide (CO) interaction on lung function and to identify biological pathways involved.
Methods
We used a two-step method for fast linear mixed model computations for genome-wide association studies, exploring whether variants modify the longitudinal relationship between 4-month average pollution and post-bronchodilator FEV
1
in 522 Caucasian and 88 African-American asthmatic children. Top hits were confirmed with classic linear mixed-effect models. We used the improved gene set enrichment analysis for GWAS (
i-GSEA4GWAS
) to identify plausible pathways.
Results
Two SNPs near the
EPHA3
(rs13090972 and rs958144) and one in
TXNDC8
(rs7041938) showed significant interactions with NO
2
in Caucasians but we did not replicate this locus in African-Americans. SNP–CO interactions did not reach genome-wide significance. The
i-GSEA4GWAS
showed a pathway linked to the HO-1/CO system to be associated with CO-related FEV
1
changes. For NO
2
-related FEV
1
responses, we identified pathways involved in cellular adhesion, oxidative stress, inflammation, and metabolic responses.
Conclusion
The host lung function response to long-term exposure to pollution is linked to genes involved in cellular adhesion, oxidative stress, inflammatory, and metabolic pathways.</description><subject>Adhesion</subject><subject>Air Pollutants - analysis</subject><subject>Air Pollutants - toxicity</subject><subject>Air pollution</subject><subject>Asthma</subject><subject>Asthma - physiopathology</subject><subject>Asthma in children</subject><subject>Bronchodilators</subject><subject>Carbon monoxide</subject><subject>Carbon Monoxide - analysis</subject><subject>Child</subject><subject>Children</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Gene set enrichment analysis</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Identification methods</subject><subject>Inflammation</subject><subject>Lung - physiopathology</subject><subject>Lungs</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic pathways</subject><subject>Metabolic response</subject><subject>Metabolism</subject><subject>Nitrogen dioxide</subject><subject>Nitrogen Dioxide - analysis</subject><subject>Oxidative stress</subject><subject>Physiological aspects</subject><subject>Pollution</subject><subject>Respiratory function</subject><subject>Respiratory Function Tests</subject><subject>Single-nucleotide polymorphism</subject><issn>1559-0631</issn><issn>1559-064X</issn><issn>1559-064X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kl1rFDEUhgdRbK3-AG9kQBBvpuZ7JldSil9Q0AsF78LZJLOTkknWZMay_96MU7ddUULISfKcN8nJW1XPMTrHiHZvMsO0RQ3CsnQqGvqgOsWcl5lg3x8eYopPqic5XyPEWCvQ4-qEYkQ60qHTSn2BabiBfQ0B_D67XMe-hnprQxxtc-OMXWJbbwrhUr2L3s-Ti6F2YbIJ9O84T7PZl5Ua8jSMMDld68F5k2x4Wj3qwWf77HY8q769f_f18mNz9fnDp8uLq0ZzIadGa007Lbno2460IAXSmjEgzHDCKCWbzrKWgwbBsDHSUE1Qp7lBzPYUOKFn1dtVdzdvRmu0DVMCr3bJjZD2KoJTxzvBDWobfyqMWooY4UXh9a1Cij9mmyc1uqyt9xBsnLMiBAvScSxRQV_-hV7HOZUCLhQThJRLyztqC94qF_pYDtaLqLrgEglJpFio839QpRk7Oh2D7V1ZP0p4dS9hsOCnIcf1V_IxiFdQp5hzsv2hGhipxT9q9Y8q_lGLfxQtOS_ul_GQ8ccwBSArkMtW2Np09_T_q_4CwJzPGw</recordid><startdate>20190601</startdate><enddate>20190601</enddate><creator>Ierodiakonou, Despo</creator><creator>Coull, Brent A.</creator><creator>Zanobetti, Antonella</creator><creator>Postma, Dirkje S.</creator><creator>Boezen, H. Marike</creator><creator>Vonk, Judith M.</creator><creator>McKone, Edward F.</creator><creator>Schildcrout, Jonathan S.</creator><creator>Koppelman, Gerard H.</creator><creator>Croteau-Chonka, Damien C.</creator><creator>Lumley, Thomas</creator><creator>Koutrakis, Petros</creator><creator>Schwartz, Joel</creator><creator>Gold, Diane R.</creator><creator>Weiss, Scott T.</creator><general>Nature Publishing Group US</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>3V.</scope><scope>7QO</scope><scope>7ST</scope><scope>7T2</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>M7S</scope><scope>P64</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>SOI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190601</creationdate><title>Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children</title><author>Ierodiakonou, Despo ; Coull, Brent A. ; Zanobetti, Antonella ; Postma, Dirkje S. ; Boezen, H. Marike ; Vonk, Judith M. ; McKone, Edward F. ; Schildcrout, Jonathan S. ; Koppelman, Gerard H. ; Croteau-Chonka, Damien C. ; Lumley, Thomas ; Koutrakis, Petros ; Schwartz, Joel ; Gold, Diane R. ; Weiss, Scott T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c569t-ccc38c956f7827a960cc44a24d524332b8e475aca641dd9d3c208c5d04ef3a523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adhesion</topic><topic>Air Pollutants - analysis</topic><topic>Air Pollutants - toxicity</topic><topic>Air pollution</topic><topic>Asthma</topic><topic>Asthma - physiopathology</topic><topic>Asthma in children</topic><topic>Bronchodilators</topic><topic>Carbon monoxide</topic><topic>Carbon Monoxide - analysis</topic><topic>Child</topic><topic>Children</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Gene set enrichment analysis</topic><topic>Genetic aspects</topic><topic>Genetics</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Identification methods</topic><topic>Inflammation</topic><topic>Lung - physiopathology</topic><topic>Lungs</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic pathways</topic><topic>Metabolic response</topic><topic>Metabolism</topic><topic>Nitrogen dioxide</topic><topic>Nitrogen Dioxide - analysis</topic><topic>Oxidative stress</topic><topic>Physiological aspects</topic><topic>Pollution</topic><topic>Respiratory function</topic><topic>Respiratory Function Tests</topic><topic>Single-nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ierodiakonou, Despo</creatorcontrib><creatorcontrib>Coull, Brent A.</creatorcontrib><creatorcontrib>Zanobetti, Antonella</creatorcontrib><creatorcontrib>Postma, Dirkje S.</creatorcontrib><creatorcontrib>Boezen, H. Marike</creatorcontrib><creatorcontrib>Vonk, Judith M.</creatorcontrib><creatorcontrib>McKone, Edward F.</creatorcontrib><creatorcontrib>Schildcrout, Jonathan S.</creatorcontrib><creatorcontrib>Koppelman, Gerard H.</creatorcontrib><creatorcontrib>Croteau-Chonka, Damien C.</creatorcontrib><creatorcontrib>Lumley, Thomas</creatorcontrib><creatorcontrib>Koutrakis, Petros</creatorcontrib><creatorcontrib>Schwartz, Joel</creatorcontrib><creatorcontrib>Gold, Diane R.</creatorcontrib><creatorcontrib>Weiss, Scott T.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Environment Abstracts</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science 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 Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of exposure science & environmental epidemiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ierodiakonou, Despo</au><au>Coull, Brent A.</au><au>Zanobetti, Antonella</au><au>Postma, Dirkje S.</au><au>Boezen, H. Marike</au><au>Vonk, Judith M.</au><au>McKone, Edward F.</au><au>Schildcrout, Jonathan S.</au><au>Koppelman, Gerard H.</au><au>Croteau-Chonka, Damien C.</au><au>Lumley, Thomas</au><au>Koutrakis, Petros</au><au>Schwartz, Joel</au><au>Gold, Diane R.</au><au>Weiss, Scott T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children</atitle><jtitle>Journal of exposure science & environmental epidemiology</jtitle><stitle>J Expo Sci Environ Epidemiol</stitle><addtitle>J Expo Sci Environ Epidemiol</addtitle><date>2019-06-01</date><risdate>2019</risdate><volume>29</volume><issue>4</issue><spage>539</spage><epage>547</epage><pages>539-547</pages><issn>1559-0631</issn><issn>1559-064X</issn><eissn>1559-064X</eissn><abstract>Objectives
We aimed to investigate the role of genetics in the respiratory response of asthmatic children to air pollution, with a genome-wide level analysis of gene by nitrogen dioxide (NO
2
) and carbon monoxide (CO) interaction on lung function and to identify biological pathways involved.
Methods
We used a two-step method for fast linear mixed model computations for genome-wide association studies, exploring whether variants modify the longitudinal relationship between 4-month average pollution and post-bronchodilator FEV
1
in 522 Caucasian and 88 African-American asthmatic children. Top hits were confirmed with classic linear mixed-effect models. We used the improved gene set enrichment analysis for GWAS (
i-GSEA4GWAS
) to identify plausible pathways.
Results
Two SNPs near the
EPHA3
(rs13090972 and rs958144) and one in
TXNDC8
(rs7041938) showed significant interactions with NO
2
in Caucasians but we did not replicate this locus in African-Americans. SNP–CO interactions did not reach genome-wide significance. The
i-GSEA4GWAS
showed a pathway linked to the HO-1/CO system to be associated with CO-related FEV
1
changes. For NO
2
-related FEV
1
responses, we identified pathways involved in cellular adhesion, oxidative stress, inflammation, and metabolic responses.
Conclusion
The host lung function response to long-term exposure to pollution is linked to genes involved in cellular adhesion, oxidative stress, inflammatory, and metabolic pathways.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>31028280</pmid><doi>10.1038/s41370-019-0136-3</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1559-0631 |
| ispartof | Journal of exposure science & environmental epidemiology, 2019-06, Vol.29 (4), p.539-547 |
| issn | 1559-0631 1559-064X 1559-064X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10730425 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adhesion Air Pollutants - analysis Air Pollutants - toxicity Air pollution Asthma Asthma - physiopathology Asthma in children Bronchodilators Carbon monoxide Carbon Monoxide - analysis Child Children Epidemiology Female Gene set enrichment analysis Genetic aspects Genetics Genome-wide association studies Genome-Wide Association Study Genomes Health aspects Humans Identification methods Inflammation Lung - physiopathology Lungs Male Medicine Medicine & Public Health Metabolic pathways Metabolic response Metabolism Nitrogen dioxide Nitrogen Dioxide - analysis Oxidative stress Physiological aspects Pollution Respiratory function Respiratory Function Tests Single-nucleotide polymorphism |
| title | Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T22%3A17%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pathway%20analysis%20of%20a%20genome-wide%20gene%20by%20air%20pollution%20interaction%20study%20in%20asthmatic%20children&rft.jtitle=Journal%20of%20exposure%20science%20&%20environmental%20epidemiology&rft.au=Ierodiakonou,%20Despo&rft.date=2019-06-01&rft.volume=29&rft.issue=4&rft.spage=539&rft.epage=547&rft.pages=539-547&rft.issn=1559-0631&rft.eissn=1559-064X&rft_id=info:doi/10.1038/s41370-019-0136-3&rft_dat=%3Cgale_pubme%3EA590692969%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2246225249&rft_id=info:pmid/31028280&rft_galeid=A590692969&rfr_iscdi=true |