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 D. 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. HanselKathleen Barnes, Benjamin Raby, Kelan G. Tantisira, Scott T. Weiss

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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
Issue number1
StatePublished - Aug 28 2013

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'ITGB5 and AGFG1 variants are associated with severity of airway responsiveness'. Together they form a unique fingerprint.

Cite this