ITGB5 and AGFG1 variants are associated with severity of airway responsiveness

Blanca E. Himes, Weiliang Qiu, Barbara Klanderman, John Ziniti, Jody Senter-Sylvia, Stanley J. Szefler, Robert F. Lemanske, Robert S. Zeiger, Robert C. Strunk, Fernando Martinez, Homer Boushey, Vernon M. Chinchilli, Elliot Israel, David Mauger, Gerard H. Koppelman, Maartje A E Nieuwenhuis, Dirkje S. Postma, Judith M. Vonk, Nicholas Rafaels, Nadia N. Hansel & 4 others Kathleen Barnes, Benjamin Raby, Kelan G. Tantisira, Scott T. Weiss

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Article number86
JournalBMC Medical Genetics
Volume14
Issue number1
DOIs
StatePublished - Aug 28 2013

Fingerprint

Single Nucleotide Polymorphism
Genome-Wide Association Study
Linear Models
HapMap Project
Genes
Methacholine Chloride
Smooth Muscle
Asthma
Clinical Trials
Pharmaceutical Preparations
Population

Keywords

  • AGFG1
  • Airway hyperresponsiveness
  • Asthma
  • Genome-wide association study
  • ITGB5

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Himes, B. E., Qiu, W., Klanderman, B., Ziniti, J., Senter-Sylvia, J., Szefler, S. J., ... Weiss, S. T. (2013). ITGB5 and AGFG1 variants are associated with severity of airway responsiveness. BMC Medical Genetics, 14(1), [86]. https://doi.org/10.1186/1471-2350-14-86

ITGB5 and AGFG1 variants are associated with severity of airway responsiveness. / Himes, Blanca E.; Qiu, Weiliang; Klanderman, Barbara; Ziniti, John; Senter-Sylvia, Jody; Szefler, Stanley J.; Lemanske, Robert F.; Zeiger, Robert S.; Strunk, Robert C.; Martinez, Fernando; Boushey, Homer; Chinchilli, Vernon M.; Israel, Elliot; Mauger, David; Koppelman, Gerard H.; Nieuwenhuis, Maartje A E; Postma, Dirkje S.; Vonk, Judith M.; Rafaels, Nicholas; Hansel, Nadia N.; Barnes, Kathleen; Raby, Benjamin; Tantisira, Kelan G.; Weiss, Scott T.

In: BMC Medical Genetics, Vol. 14, No. 1, 86, 28.08.2013.

Research output: Contribution to journalArticle

Himes, BE, Qiu, W, Klanderman, B, Ziniti, J, Senter-Sylvia, J, Szefler, SJ, Lemanske, RF, Zeiger, RS, Strunk, RC, Martinez, F, Boushey, H, Chinchilli, VM, Israel, E, Mauger, D, Koppelman, GH, Nieuwenhuis, MAE, Postma, DS, Vonk, JM, Rafaels, N, Hansel, NN, Barnes, K, Raby, B, Tantisira, KG & Weiss, ST 2013, 'ITGB5 and AGFG1 variants are associated with severity of airway responsiveness', BMC Medical Genetics, vol. 14, no. 1, 86. https://doi.org/10.1186/1471-2350-14-86
Himes BE, Qiu W, Klanderman B, Ziniti J, Senter-Sylvia J, Szefler SJ et al. ITGB5 and AGFG1 variants are associated with severity of airway responsiveness. BMC Medical Genetics. 2013 Aug 28;14(1). 86. https://doi.org/10.1186/1471-2350-14-86
Himes, Blanca E. ; Qiu, Weiliang ; Klanderman, Barbara ; Ziniti, John ; Senter-Sylvia, Jody ; Szefler, Stanley J. ; Lemanske, Robert F. ; Zeiger, Robert S. ; Strunk, Robert C. ; Martinez, Fernando ; Boushey, Homer ; Chinchilli, Vernon M. ; Israel, Elliot ; Mauger, David ; Koppelman, Gerard H. ; Nieuwenhuis, Maartje A E ; Postma, Dirkje S. ; Vonk, Judith M. ; Rafaels, Nicholas ; Hansel, Nadia N. ; Barnes, Kathleen ; Raby, Benjamin ; Tantisira, Kelan G. ; Weiss, Scott T. / ITGB5 and AGFG1 variants are associated with severity of airway responsiveness. In: BMC Medical Genetics. 2013 ; Vol. 14, No. 1.
@article{47381e91378f48d8855d35ba50e89581,
title = "ITGB5 and AGFG1 variants are associated with severity of airway responsiveness",
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.",
keywords = "AGFG1, Airway hyperresponsiveness, Asthma, Genome-wide association study, ITGB5",
author = "Himes, {Blanca E.} and Weiliang Qiu and Barbara Klanderman and John Ziniti and Jody Senter-Sylvia and Szefler, {Stanley J.} and Lemanske, {Robert F.} and Zeiger, {Robert S.} and Strunk, {Robert C.} and Fernando Martinez and Homer Boushey and Chinchilli, {Vernon M.} and Elliot Israel and David Mauger and Koppelman, {Gerard H.} and Nieuwenhuis, {Maartje A E} and Postma, {Dirkje S.} and Vonk, {Judith M.} and Nicholas Rafaels and Hansel, {Nadia N.} and Kathleen Barnes and Benjamin Raby and Tantisira, {Kelan G.} and Weiss, {Scott T.}",
year = "2013",
month = "8",
day = "28",
doi = "10.1186/1471-2350-14-86",
language = "English (US)",
volume = "14",
journal = "BMC Medical Genetics",
issn = "1471-2350",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - ITGB5 and AGFG1 variants are associated with severity of airway responsiveness

AU - Himes, Blanca E.

AU - Qiu, Weiliang

AU - Klanderman, Barbara

AU - Ziniti, John

AU - Senter-Sylvia, Jody

AU - Szefler, Stanley J.

AU - Lemanske, Robert F.

AU - Zeiger, Robert S.

AU - Strunk, Robert C.

AU - Martinez, Fernando

AU - Boushey, Homer

AU - Chinchilli, Vernon M.

AU - Israel, Elliot

AU - Mauger, David

AU - Koppelman, Gerard H.

AU - Nieuwenhuis, Maartje A E

AU - Postma, Dirkje S.

AU - Vonk, Judith M.

AU - Rafaels, Nicholas

AU - Hansel, Nadia N.

AU - Barnes, Kathleen

AU - Raby, Benjamin

AU - Tantisira, Kelan G.

AU - Weiss, Scott T.

PY - 2013/8/28

Y1 - 2013/8/28

N2 - 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.

AB - 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.

KW - AGFG1

KW - Airway hyperresponsiveness

KW - Asthma

KW - Genome-wide association study

KW - ITGB5

UR - http://www.scopus.com/inward/record.url?scp=84883116782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883116782&partnerID=8YFLogxK

U2 - 10.1186/1471-2350-14-86

DO - 10.1186/1471-2350-14-86

M3 - Article

VL - 14

JO - BMC Medical Genetics

JF - BMC Medical Genetics

SN - 1471-2350

IS - 1

M1 - 86

ER -