Assessing the validity of asthma associations for eight candidate genes and age at diagnosis effects
Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in clo...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-09, Vol.8 (9), p.e73157 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 9 |
| container_start_page | e73157 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Pino-Yanes, María Corrales, Almudena Cumplido, José Poza, Paloma Sánchez-Machín, Inmaculada Sánchez-Palacios, Anselmo Figueroa, Javier Acosta-Fernández, Orlando Buset, Nisa García-Robaina, José Carlos Hernández, Mariano Villar, Jesús Carrillo, Teresa Flores, Carlos |
| description | Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis.
We systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition, in silico replication with GWAS data supported the association of IL4R.
Our results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found. |
| doi_str_mv | 10.1371/journal.pone.0073157 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1431102566</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A478353249</galeid><doaj_id>oai_doaj_org_article_c6933645c3d64192a6360ed7301f5ac7</doaj_id><sourcerecordid>A478353249</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-362429152f64c9e0835992d6c5e43928bb274d1dbe7734df2ab998b876cce83b3</originalsourceid><addsrcrecordid>eNqNk0tr3DAQx01padK036C0gkJpD7u1HpasS2EJfSwEAn1dhSyNbS1ea2vJofn21e46YV1yKDpIGv3mP9JoJste4nyJqcAfNn4cet0td76HZZ4LigvxKDvHkpIFJzl9fLI-y56FsMnzgpacP83OCMupLEV5ntlVCBCC6xsUW0A3unPWxVvka6RDbLc6TcEbp6PzfUC1HxC4po3I6N46qyOgBnoIKG2RbgDpiKzTTe-DCwjqGkwMz7Mnte4CvJjmi-zn508_Lr8urq6_rC9XVwsjijIuKCeMSFyQmjMjIS9pISWx3BTAqCRlVRHBLLYVCEGZrYmupCyrUnBjoKQVvcheH3V3nQ9qSlBQmFGMc1Jwnoj1kbBeb9RucFs93CqvnToY_NAoPURnOlCGS0o5Kwy1nGFJNKc8BytojutCG5G0Pk7RxmoL1kAfB93NROcnvWtV428UFVyUhCWBd5PA4H-PEKLaumCg63QPfjzcmxLOS1om9M0_6MOvm6hGpwe4vvYprtmLqhUTKZ2UMJmo5QNUGha2zqRqql2yzxzezxwSE-FPbPQYglp___b_7PWvOfv2hG1Bd7ENvhsPpTYH2RE0gw9hgPo-yThX-2a4y4baN4OamiG5vTr9oHunu-qnfwGKaAOE</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1431102566</pqid></control><display><type>article</type><title>Assessing the validity of asthma associations for eight candidate genes and age at diagnosis effects</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Pino-Yanes, María ; Corrales, Almudena ; Cumplido, José ; Poza, Paloma ; Sánchez-Machín, Inmaculada ; Sánchez-Palacios, Anselmo ; Figueroa, Javier ; Acosta-Fernández, Orlando ; Buset, Nisa ; García-Robaina, José Carlos ; Hernández, Mariano ; Villar, Jesús ; Carrillo, Teresa ; Flores, Carlos</creator><contributor>Colombo, Gualtiero I.</contributor><creatorcontrib>Pino-Yanes, María ; Corrales, Almudena ; Cumplido, José ; Poza, Paloma ; Sánchez-Machín, Inmaculada ; Sánchez-Palacios, Anselmo ; Figueroa, Javier ; Acosta-Fernández, Orlando ; Buset, Nisa ; García-Robaina, José Carlos ; Hernández, Mariano ; Villar, Jesús ; Carrillo, Teresa ; Flores, Carlos ; Colombo, Gualtiero I.</creatorcontrib><description>Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis.
We systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition, in silico replication with GWAS data supported the association of IL4R.
Our results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0073157</identifier><identifier>PMID: 24039878</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>ADAM Proteins - genetics ; Adolescent ; Adult ; Age ; Age factors ; Alleles ; Allergies ; Asthma ; Asthma - diagnosis ; Asthma - genetics ; Atopy ; Case-Control Studies ; CD14 antigen ; Child ; Chromosome Mapping ; Diagnosis ; Disease susceptibility ; Gene Frequency ; Genes ; Genetic aspects ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genetics ; Genome-wide association studies ; Genomes ; Genomics ; Genotype ; Hospitals ; Humans ; Interleukin 1 ; Interleukin 13 ; Interleukin 4 ; Interleukin 4 receptors ; Interleukin-4 Receptor alpha Subunit - genetics ; Laboratories ; Medical diagnosis ; Odds Ratio ; Polymorphism, Single Nucleotide ; Receptors, IgE - genetics ; Reproducibility ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Studies ; Tumor necrosis factor ; Tumor necrosis factor-TNF ; Young Adult</subject><ispartof>PloS one, 2013-09, Vol.8 (9), p.e73157</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Pino-Yanes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Pino-Yanes et al 2013 Pino-Yanes et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-362429152f64c9e0835992d6c5e43928bb274d1dbe7734df2ab998b876cce83b3</citedby><cites>FETCH-LOGICAL-c758t-362429152f64c9e0835992d6c5e43928bb274d1dbe7734df2ab998b876cce83b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767824/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767824/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23849,27907,27908,53774,53776,79351,79352</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24039878$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Colombo, Gualtiero I.</contributor><creatorcontrib>Pino-Yanes, María</creatorcontrib><creatorcontrib>Corrales, Almudena</creatorcontrib><creatorcontrib>Cumplido, José</creatorcontrib><creatorcontrib>Poza, Paloma</creatorcontrib><creatorcontrib>Sánchez-Machín, Inmaculada</creatorcontrib><creatorcontrib>Sánchez-Palacios, Anselmo</creatorcontrib><creatorcontrib>Figueroa, Javier</creatorcontrib><creatorcontrib>Acosta-Fernández, Orlando</creatorcontrib><creatorcontrib>Buset, Nisa</creatorcontrib><creatorcontrib>García-Robaina, José Carlos</creatorcontrib><creatorcontrib>Hernández, Mariano</creatorcontrib><creatorcontrib>Villar, Jesús</creatorcontrib><creatorcontrib>Carrillo, Teresa</creatorcontrib><creatorcontrib>Flores, Carlos</creatorcontrib><title>Assessing the validity of asthma associations for eight candidate genes and age at diagnosis effects</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis.
We systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition, in silico replication with GWAS data supported the association of IL4R.
Our results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.</description><subject>ADAM Proteins - genetics</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Age factors</subject><subject>Alleles</subject><subject>Allergies</subject><subject>Asthma</subject><subject>Asthma - diagnosis</subject><subject>Asthma - genetics</subject><subject>Atopy</subject><subject>Case-Control Studies</subject><subject>CD14 antigen</subject><subject>Child</subject><subject>Chromosome Mapping</subject><subject>Diagnosis</subject><subject>Disease susceptibility</subject><subject>Gene Frequency</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics</subject><subject>Genome-wide association studies</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Interleukin 1</subject><subject>Interleukin 13</subject><subject>Interleukin 4</subject><subject>Interleukin 4 receptors</subject><subject>Interleukin-4 Receptor alpha Subunit - genetics</subject><subject>Laboratories</subject><subject>Medical diagnosis</subject><subject>Odds Ratio</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptors, IgE - genetics</subject><subject>Reproducibility</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><subject>Tumor necrosis factor</subject><subject>Tumor necrosis factor-TNF</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</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>eNqNk0tr3DAQx01padK036C0gkJpD7u1HpasS2EJfSwEAn1dhSyNbS1ea2vJofn21e46YV1yKDpIGv3mP9JoJste4nyJqcAfNn4cet0td76HZZ4LigvxKDvHkpIFJzl9fLI-y56FsMnzgpacP83OCMupLEV5ntlVCBCC6xsUW0A3unPWxVvka6RDbLc6TcEbp6PzfUC1HxC4po3I6N46qyOgBnoIKG2RbgDpiKzTTe-DCwjqGkwMz7Mnte4CvJjmi-zn508_Lr8urq6_rC9XVwsjijIuKCeMSFyQmjMjIS9pISWx3BTAqCRlVRHBLLYVCEGZrYmupCyrUnBjoKQVvcheH3V3nQ9qSlBQmFGMc1Jwnoj1kbBeb9RucFs93CqvnToY_NAoPURnOlCGS0o5Kwy1nGFJNKc8BytojutCG5G0Pk7RxmoL1kAfB93NROcnvWtV428UFVyUhCWBd5PA4H-PEKLaumCg63QPfjzcmxLOS1om9M0_6MOvm6hGpwe4vvYprtmLqhUTKZ2UMJmo5QNUGha2zqRqql2yzxzezxwSE-FPbPQYglp___b_7PWvOfv2hG1Bd7ENvhsPpTYH2RE0gw9hgPo-yThX-2a4y4baN4OamiG5vTr9oHunu-qnfwGKaAOE</recordid><startdate>20130909</startdate><enddate>20130909</enddate><creator>Pino-Yanes, María</creator><creator>Corrales, Almudena</creator><creator>Cumplido, José</creator><creator>Poza, Paloma</creator><creator>Sánchez-Machín, Inmaculada</creator><creator>Sánchez-Palacios, Anselmo</creator><creator>Figueroa, Javier</creator><creator>Acosta-Fernández, Orlando</creator><creator>Buset, Nisa</creator><creator>García-Robaina, José Carlos</creator><creator>Hernández, Mariano</creator><creator>Villar, Jesús</creator><creator>Carrillo, Teresa</creator><creator>Flores, Carlos</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>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</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>ARAPS</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>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130909</creationdate><title>Assessing the validity of asthma associations for eight candidate genes and age at diagnosis effects</title><author>Pino-Yanes, María ; Corrales, Almudena ; Cumplido, José ; Poza, Paloma ; Sánchez-Machín, Inmaculada ; Sánchez-Palacios, Anselmo ; Figueroa, Javier ; Acosta-Fernández, Orlando ; Buset, Nisa ; García-Robaina, José Carlos ; Hernández, Mariano ; Villar, Jesús ; Carrillo, Teresa ; Flores, Carlos</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-362429152f64c9e0835992d6c5e43928bb274d1dbe7734df2ab998b876cce83b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>ADAM Proteins - genetics</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Age factors</topic><topic>Alleles</topic><topic>Allergies</topic><topic>Asthma</topic><topic>Asthma - diagnosis</topic><topic>Asthma - genetics</topic><topic>Atopy</topic><topic>Case-Control Studies</topic><topic>CD14 antigen</topic><topic>Child</topic><topic>Chromosome Mapping</topic><topic>Diagnosis</topic><topic>Disease susceptibility</topic><topic>Gene Frequency</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Association Studies</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics</topic><topic>Genome-wide association studies</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Genotype</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Interleukin 1</topic><topic>Interleukin 13</topic><topic>Interleukin 4</topic><topic>Interleukin 4 receptors</topic><topic>Interleukin-4 Receptor alpha Subunit - genetics</topic><topic>Laboratories</topic><topic>Medical diagnosis</topic><topic>Odds Ratio</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptors, IgE - genetics</topic><topic>Reproducibility</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Studies</topic><topic>Tumor necrosis factor</topic><topic>Tumor necrosis factor-TNF</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pino-Yanes, María</creatorcontrib><creatorcontrib>Corrales, Almudena</creatorcontrib><creatorcontrib>Cumplido, José</creatorcontrib><creatorcontrib>Poza, Paloma</creatorcontrib><creatorcontrib>Sánchez-Machín, Inmaculada</creatorcontrib><creatorcontrib>Sánchez-Palacios, Anselmo</creatorcontrib><creatorcontrib>Figueroa, Javier</creatorcontrib><creatorcontrib>Acosta-Fernández, Orlando</creatorcontrib><creatorcontrib>Buset, Nisa</creatorcontrib><creatorcontrib>García-Robaina, José Carlos</creatorcontrib><creatorcontrib>Hernández, Mariano</creatorcontrib><creatorcontrib>Villar, Jesús</creatorcontrib><creatorcontrib>Carrillo, Teresa</creatorcontrib><creatorcontrib>Flores, Carlos</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: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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 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>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content 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>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pino-Yanes, María</au><au>Corrales, Almudena</au><au>Cumplido, José</au><au>Poza, Paloma</au><au>Sánchez-Machín, Inmaculada</au><au>Sánchez-Palacios, Anselmo</au><au>Figueroa, Javier</au><au>Acosta-Fernández, Orlando</au><au>Buset, Nisa</au><au>García-Robaina, José Carlos</au><au>Hernández, Mariano</au><au>Villar, Jesús</au><au>Carrillo, Teresa</au><au>Flores, Carlos</au><au>Colombo, Gualtiero I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessing the validity of asthma associations for eight candidate genes and age at diagnosis effects</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-09-09</date><risdate>2013</risdate><volume>8</volume><issue>9</issue><spage>e73157</spage><pages>e73157-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis.
We systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition, in silico replication with GWAS data supported the association of IL4R.
Our results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24039878</pmid><doi>10.1371/journal.pone.0073157</doi><tpages>e73157</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-09, Vol.8 (9), p.e73157 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1431102566 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | ADAM Proteins - genetics Adolescent Adult Age Age factors Alleles Allergies Asthma Asthma - diagnosis Asthma - genetics Atopy Case-Control Studies CD14 antigen Child Chromosome Mapping Diagnosis Disease susceptibility Gene Frequency Genes Genetic aspects Genetic Association Studies Genetic Predisposition to Disease Genetics Genome-wide association studies Genomes Genomics Genotype Hospitals Humans Interleukin 1 Interleukin 13 Interleukin 4 Interleukin 4 receptors Interleukin-4 Receptor alpha Subunit - genetics Laboratories Medical diagnosis Odds Ratio Polymorphism, Single Nucleotide Receptors, IgE - genetics Reproducibility Single nucleotide polymorphisms Single-nucleotide polymorphism Studies Tumor necrosis factor Tumor necrosis factor-TNF Young Adult |
| title | Assessing the validity of asthma associations for eight candidate genes and age at diagnosis effects |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T13%3A02%3A36IST&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=Assessing%20the%20validity%20of%20asthma%20associations%20for%20eight%20candidate%20genes%20and%20age%20at%20diagnosis%20effects&rft.jtitle=PloS%20one&rft.au=Pino-Yanes,%20Mar%C3%ADa&rft.date=2013-09-09&rft.volume=8&rft.issue=9&rft.spage=e73157&rft.pages=e73157-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0073157&rft_dat=%3Cgale_plos_%3EA478353249%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=1431102566&rft_id=info:pmid/24039878&rft_galeid=A478353249&rft_doaj_id=oai_doaj_org_article_c6933645c3d64192a6360ed7301f5ac7&rfr_iscdi=true |