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A genome-wide association study to identify genetic determinants of atopy in subjects from the United Kingdom

A genome-wide association study to identify genetic determinants of atopy in subjects from the United Kingdom
A genome-wide association study to identify genetic determinants of atopy in subjects from the United Kingdom
Background: A genetic component in the development of atopy has been identified. However, numerous heritability models have been proposed with inconsistent replication of susceptibility loci and genes.

Objective: We sought to use a genome-wide association study approach to examine genetic susceptibility to atopy, which was defined as increased specific IgE levels, positive skin prick test (SPT) responses, or both, within a large discovery cohort and 3 additional white populations.

Methods: Single nucleotide polymorphisms (SNPs) across the genome were tested for association with increased specific IgE levels (?0.35 kUA/L) in the British 1958 Birth Cohort (1083 cases and 2770 control subjects; Illumina 550K Array) to 1 or more allergens, including house dust mite (Der p 1), mixed grass, or cat fur. Independent replication of identified loci (P ? .05) was assessed in 3 case-control cohorts from the United Kingdom (n = 3225). Combined analyses of data for top signals across cohorts were conducted for atopic phenotypes: increased specific IgE levels (1378 cases and 3151 control subjects) and positive SPT responses (1058 cases and 2167 control subjects).

Results: A single SNP on chromosome 13q14 met genome-wide significance (P = 2.15 × 10?9), and a further 6 loci (4.50 × 10?7 ? P ? 5.00 × 10?5) showed weaker evidence for association with increased specific IgE levels in the British 1958 Birth Cohort. However, no SNPs studied showed consistent association with atopy defined by increased specific IgE levels, positive SPT responses, or both in all study cohorts.

Conclusions: Seven putative atopy loci were identified using a genome-wide association study approach but showed limited replication across several white populations. This study suggests that large-scale analyses with results from multiple populations will be needed to reliably identify key genetic factors underlying atopy predisposition.
atopy, specific ige, skin prick test, genome-wide association study, british 1958 birth cohort
0091-6749
223-231
Wan, Yize I.
73af5680-19a0-4dca-b214-bb94aac4f2ca
Strachan, David P.
76ddbacc-b6cb-48db-8ab6-77f799c8d1c8
Evans, David M.
7adf29d1-837e-4c60-8e1c-247dc8e3b68b
Henderson, John
dcb5516b-cca2-49b5-8a17-f4cf707daa36
McKeever, Tricia
b06bca95-4829-409f-8331-44d424f9c4b3
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Hall, Ian P.
744f8a77-0d2f-49a5-a01a-f9f801fe6d24
Sayers, Ian
8595fc2e-102b-406c-ba26-269b8bdba786
Wan, Yize I.
73af5680-19a0-4dca-b214-bb94aac4f2ca
Strachan, David P.
76ddbacc-b6cb-48db-8ab6-77f799c8d1c8
Evans, David M.
7adf29d1-837e-4c60-8e1c-247dc8e3b68b
Henderson, John
dcb5516b-cca2-49b5-8a17-f4cf707daa36
McKeever, Tricia
b06bca95-4829-409f-8331-44d424f9c4b3
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Hall, Ian P.
744f8a77-0d2f-49a5-a01a-f9f801fe6d24
Sayers, Ian
8595fc2e-102b-406c-ba26-269b8bdba786

Wan, Yize I., Strachan, David P., Evans, David M., Henderson, John, McKeever, Tricia, Holloway, John W., Hall, Ian P. and Sayers, Ian (2011) A genome-wide association study to identify genetic determinants of atopy in subjects from the United Kingdom. Journal of Allergy and Clinical Immunology, 127 (1), 223-231. (doi:10.1016/j.jaci.2010.10.006). (PMID:21094521)

Record type: Article

Abstract

Background: A genetic component in the development of atopy has been identified. However, numerous heritability models have been proposed with inconsistent replication of susceptibility loci and genes.

Objective: We sought to use a genome-wide association study approach to examine genetic susceptibility to atopy, which was defined as increased specific IgE levels, positive skin prick test (SPT) responses, or both, within a large discovery cohort and 3 additional white populations.

Methods: Single nucleotide polymorphisms (SNPs) across the genome were tested for association with increased specific IgE levels (?0.35 kUA/L) in the British 1958 Birth Cohort (1083 cases and 2770 control subjects; Illumina 550K Array) to 1 or more allergens, including house dust mite (Der p 1), mixed grass, or cat fur. Independent replication of identified loci (P ? .05) was assessed in 3 case-control cohorts from the United Kingdom (n = 3225). Combined analyses of data for top signals across cohorts were conducted for atopic phenotypes: increased specific IgE levels (1378 cases and 3151 control subjects) and positive SPT responses (1058 cases and 2167 control subjects).

Results: A single SNP on chromosome 13q14 met genome-wide significance (P = 2.15 × 10?9), and a further 6 loci (4.50 × 10?7 ? P ? 5.00 × 10?5) showed weaker evidence for association with increased specific IgE levels in the British 1958 Birth Cohort. However, no SNPs studied showed consistent association with atopy defined by increased specific IgE levels, positive SPT responses, or both in all study cohorts.

Conclusions: Seven putative atopy loci were identified using a genome-wide association study approach but showed limited replication across several white populations. This study suggests that large-scale analyses with results from multiple populations will be needed to reliably identify key genetic factors underlying atopy predisposition.

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More information

Accepted/In Press date: 19 November 2010
Published date: January 2011
Keywords: atopy, specific ige, skin prick test, genome-wide association study, british 1958 birth cohort

Identifiers

Local EPrints ID: 169275
URI: http://eprints.soton.ac.uk/id/eprint/169275
ISSN: 0091-6749
PURE UUID: 2baac933-2318-4f77-8c6f-2085595f3e4f
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 13 Dec 2010 13:56
Last modified: 14 Mar 2024 02:41

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Contributors

Author: Yize I. Wan
Author: David P. Strachan
Author: David M. Evans
Author: John Henderson
Author: Tricia McKeever
Author: Ian P. Hall
Author: Ian Sayers

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