ITGB5 and AGFG1 variants are associated with severity of airway responsiveness

Persistent Link:
http://hdl.handle.net/10150/610036
Title:
ITGB5 and AGFG1 variants are associated with severity of airway responsiveness
Author:
Himes, Blanca; Qiu, Weiliang; Klanderman, Barbara; Ziniti, John; Senter-Sylvia, Jody; Szefler, Stanley; Lemanske, Jr, Robert; Zeiger, Robert; Strunk, Robert; Martinez, Fernando; Boushey, Homer; Chinchilli, Vernon; Israel, Elliot; Mauger, David; Koppelman, Gerard; Nieuwenhuis, Maartje; Postma, Dirkje; Vonk, Judith; Rafaels, Nicholas; Hansel, Nadia; Barnes, Kathleen; Raby, Benjamin; Tantisira, Kelan; Weiss, Scott
Affiliation:
Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Partners HealthCare Center for Personalized Genetic Medicine and Harvard Medical School, Boston, MA, USA; Children’s Hospital Informatics Program, Boston, MA, USA; National Jewish Health and University of Colorado Denver School of Medicine, Denver, CO, USA; University of Wisconsin, Clinical Science Center, Madison, WI, USA; Kaiser Permanente Southern California Region, San Diego, CA, USA; Washington University School of Medicine, St. Louis, MO, USA; Arizona Respiratory Center, University of Arizona, College of Medicine, Tucson, AZ, USA; Division of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, University of California at San Francisco, San Francisco, CA, USA; Department of Biostatistics, Penn State College of Medicine, Hershey, PA, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pulmonology and Tuberculosis, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Epidemiology, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
Issue Date:
2013
Publisher:
BioMed Central
Citation:
Himes et al. BMC Medical Genetics 2013, 14:86 http://www.biomedcentral.com/1471-2350/14/86
Journal:
BMC Medical Genetics
Rights:
© 2013 Himes et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:Airway hyperresponsiveness (AHR), a primary characteristic of asthma, involves increased airway smooth muscle contractility in response to certain exposures. We sought to determine whether common genetic variants were associated with AHR severity.METHODS:A genome-wide association study (GWAS) of AHR, quantified as the natural log of the dosage of methacholine causing a 20% drop in FEV1, was performed with 994 non-Hispanic white asthmatic subjects from three drug clinical trials: CAMP, CARE, and ACRN. Genotyping was performed on Affymetrix 6.0 arrays, and imputed data based on HapMap Phase 2, was used to measure the association of SNPs with AHR using a linear regression model. Replication of primary findings was attempted in 650 white subjects from DAG, and 3,354 white subjects from LHS. Evidence that the top SNPs were eQTL of their respective genes was sought using expression data available for 419 white CAMP subjects.RESULTS:The top primary GWAS associations were in rs848788 (P-value 7.2E-07) and rs6731443 (P-value 2.5E-06), located within the ITGB5 and AGFG1 genes, respectively. The AGFG1 result replicated at a nominally significant level in one independent population (LHS P-value 0.012), and the SNP had a nominally significant unadjusted P-value (0.0067) for being an eQTL of AGFG1.CONCLUSIONS:Based on current knowledge of ITGB5 and AGFG1, our results suggest that variants within these genes may be involved in modulating AHR. Future functional studies are required to confirm that our associations represent true biologically significant findings.
EISSN:
1471-2350
DOI:
10.1186/1471-2350-14-86
Keywords:
Asthma; Airway hyperresponsiveness; Genome-wide association study; ITGB5; AGFG1
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1471-2350/14/86

Full metadata record

DC FieldValue Language
dc.contributor.authorHimes, Blancaen
dc.contributor.authorQiu, Weiliangen
dc.contributor.authorKlanderman, Barbaraen
dc.contributor.authorZiniti, Johnen
dc.contributor.authorSenter-Sylvia, Jodyen
dc.contributor.authorSzefler, Stanleyen
dc.contributor.authorLemanske, Jr, Roberten
dc.contributor.authorZeiger, Roberten
dc.contributor.authorStrunk, Roberten
dc.contributor.authorMartinez, Fernandoen
dc.contributor.authorBoushey, Homeren
dc.contributor.authorChinchilli, Vernonen
dc.contributor.authorIsrael, Ellioten
dc.contributor.authorMauger, Daviden
dc.contributor.authorKoppelman, Gerarden
dc.contributor.authorNieuwenhuis, Maartjeen
dc.contributor.authorPostma, Dirkjeen
dc.contributor.authorVonk, Judithen
dc.contributor.authorRafaels, Nicholasen
dc.contributor.authorHansel, Nadiaen
dc.contributor.authorBarnes, Kathleenen
dc.contributor.authorRaby, Benjaminen
dc.contributor.authorTantisira, Kelanen
dc.contributor.authorWeiss, Scotten
dc.date.accessioned2016-05-20T08:57:05Z-
dc.date.available2016-05-20T08:57:05Z-
dc.date.issued2013en
dc.identifier.citationHimes et al. BMC Medical Genetics 2013, 14:86 http://www.biomedcentral.com/1471-2350/14/86en
dc.identifier.doi10.1186/1471-2350-14-86en
dc.identifier.urihttp://hdl.handle.net/10150/610036-
dc.description.abstractBACKGROUND:Airway hyperresponsiveness (AHR), a primary characteristic of asthma, involves increased airway smooth muscle contractility in response to certain exposures. We sought to determine whether common genetic variants were associated with AHR severity.METHODS:A genome-wide association study (GWAS) of AHR, quantified as the natural log of the dosage of methacholine causing a 20% drop in FEV1, was performed with 994 non-Hispanic white asthmatic subjects from three drug clinical trials: CAMP, CARE, and ACRN. Genotyping was performed on Affymetrix 6.0 arrays, and imputed data based on HapMap Phase 2, was used to measure the association of SNPs with AHR using a linear regression model. Replication of primary findings was attempted in 650 white subjects from DAG, and 3,354 white subjects from LHS. Evidence that the top SNPs were eQTL of their respective genes was sought using expression data available for 419 white CAMP subjects.RESULTS:The top primary GWAS associations were in rs848788 (P-value 7.2E-07) and rs6731443 (P-value 2.5E-06), located within the ITGB5 and AGFG1 genes, respectively. The AGFG1 result replicated at a nominally significant level in one independent population (LHS P-value 0.012), and the SNP had a nominally significant unadjusted P-value (0.0067) for being an eQTL of AGFG1.CONCLUSIONS:Based on current knowledge of ITGB5 and AGFG1, our results suggest that variants within these genes may be involved in modulating AHR. Future functional studies are required to confirm that our associations represent true biologically significant findings.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.biomedcentral.com/1471-2350/14/86en
dc.rights© 2013 Himes et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.subjectAsthmaen
dc.subjectAirway hyperresponsivenessen
dc.subjectGenome-wide association studyen
dc.subjectITGB5en
dc.subjectAGFG1en
dc.titleITGB5 and AGFG1 variants are associated with severity of airway responsivenessen
dc.typeArticleen
dc.identifier.eissn1471-2350en
dc.contributor.departmentChanning Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USAen
dc.contributor.departmentPartners HealthCare Center for Personalized Genetic Medicine and Harvard Medical School, Boston, MA, USAen
dc.contributor.departmentChildren’s Hospital Informatics Program, Boston, MA, USAen
dc.contributor.departmentNational Jewish Health and University of Colorado Denver School of Medicine, Denver, CO, USAen
dc.contributor.departmentUniversity of Wisconsin, Clinical Science Center, Madison, WI, USAen
dc.contributor.departmentKaiser Permanente Southern California Region, San Diego, CA, USAen
dc.contributor.departmentWashington University School of Medicine, St. Louis, MO, USAen
dc.contributor.departmentArizona Respiratory Center, University of Arizona, College of Medicine, Tucson, AZ, USAen
dc.contributor.departmentDivision of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, University of California at San Francisco, San Francisco, CA, USAen
dc.contributor.departmentDepartment of Biostatistics, Penn State College of Medicine, Hershey, PA, USAen
dc.contributor.departmentDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USAen
dc.contributor.departmentDepartment of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlandsen
dc.contributor.departmentDepartment of Pulmonology and Tuberculosis, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlandsen
dc.contributor.departmentDepartment of Epidemiology, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlandsen
dc.contributor.departmentDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USAen
dc.identifier.journalBMC Medical Geneticsen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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