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Defining the contribution of SNPs identified in asthma GWAS to clinical variables in asthmatic children

Defining the contribution of SNPs identified in asthma GWAS to clinical variables in asthmatic children
Defining the contribution of SNPs identified in asthma GWAS to clinical variables in asthmatic children
Background

Asthma genome-wide association studies (GWAS) have identified several asthma susceptibility genes with confidence; however the relative contribution of these genetic variants or single nucleotide polymorphisms (SNPs) to clinical endpoints (as opposed to disease diagnosis) remains largely unknown. Thus the aim of this study was to firstly bridge this gap in knowledge and secondly investigate whether these SNPs or those that are in linkage disequilibrium are likely to be functional candidates with respect to regulation of gene expression, using reported data from the ENCODE project.
Methods

Eleven of the key SNPs identified in eight loci from recent asthma GWAS were evaluated for association with asthma and clinical outcomes, including percent predicted FEV1, bronchial hyperresponsiveness (BHR) to methacholine, severity defined by British Thoracic Society steps and positive response to skin prick test, using the family based association test additive model in a well characterised UK cohort consisting of 370 families with at least two asthmatic children.
Results

GSDMB SNP rs2305480 (Ser311Pro) was associated with asthma diagnosis (p?=?8.9×10-4), BHR (p?=?8.2×10-4) and severity (p?=?1.5×10-4) with supporting evidence from a second GSDMB SNP rs11078927 (intronic). SNPs evaluated in IL33, IL18R1, IL1RL1, SMAD3, IL2RB, PDE4D, CRB1 and RAD50 did not show association with any phenotype tested when corrected for multiple testing. Analysis using ENCODE data provides further insight into the functional relevance of these SNPs.
Conclusions

Our results provide further support for the role of GSDMB SNPs in determining multiple asthma related phenotypes in childhood asthma including associations with lung function and disease severity
1471-2350
100
Tulah, Asif S
885b1a42-d8fe-4b1b-80d5-2f0818d7d1ab
Holloway, John W
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Sayers, Ian
8595fc2e-102b-406c-ba26-269b8bdba786
Tulah, Asif S
885b1a42-d8fe-4b1b-80d5-2f0818d7d1ab
Holloway, John W
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Sayers, Ian
8595fc2e-102b-406c-ba26-269b8bdba786

Tulah, Asif S, Holloway, John W and Sayers, Ian (2013) Defining the contribution of SNPs identified in asthma GWAS to clinical variables in asthmatic children. BMC Medical Genetics, 14 (1), 100. (doi:10.1186/1471-2350-14-100). (PMID:24066901)

Record type: Article

Abstract

Background

Asthma genome-wide association studies (GWAS) have identified several asthma susceptibility genes with confidence; however the relative contribution of these genetic variants or single nucleotide polymorphisms (SNPs) to clinical endpoints (as opposed to disease diagnosis) remains largely unknown. Thus the aim of this study was to firstly bridge this gap in knowledge and secondly investigate whether these SNPs or those that are in linkage disequilibrium are likely to be functional candidates with respect to regulation of gene expression, using reported data from the ENCODE project.
Methods

Eleven of the key SNPs identified in eight loci from recent asthma GWAS were evaluated for association with asthma and clinical outcomes, including percent predicted FEV1, bronchial hyperresponsiveness (BHR) to methacholine, severity defined by British Thoracic Society steps and positive response to skin prick test, using the family based association test additive model in a well characterised UK cohort consisting of 370 families with at least two asthmatic children.
Results

GSDMB SNP rs2305480 (Ser311Pro) was associated with asthma diagnosis (p?=?8.9×10-4), BHR (p?=?8.2×10-4) and severity (p?=?1.5×10-4) with supporting evidence from a second GSDMB SNP rs11078927 (intronic). SNPs evaluated in IL33, IL18R1, IL1RL1, SMAD3, IL2RB, PDE4D, CRB1 and RAD50 did not show association with any phenotype tested when corrected for multiple testing. Analysis using ENCODE data provides further insight into the functional relevance of these SNPs.
Conclusions

Our results provide further support for the role of GSDMB SNPs in determining multiple asthma related phenotypes in childhood asthma including associations with lung function and disease severity

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e-pub ahead of print date: 25 September 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 358062
URI: http://eprints.soton.ac.uk/id/eprint/358062
ISSN: 1471-2350
PURE UUID: acd7fdba-7575-426f-95cb-488396338ebb
ORCID for John W Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 04 Oct 2013 14:02
Last modified: 28 Oct 2023 01:42

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Contributors

Author: Asif S Tulah
Author: John W Holloway ORCID iD
Author: Ian Sayers

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