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Identification of ATPAF1 as a novel candidate gene for asthma in children

Identification of ATPAF1 as a novel candidate gene for asthma in children
Identification of ATPAF1 as a novel candidate gene for asthma in children
Background:
Asthma is a common disease of children with a complex genetic origin. Understanding the genetic basis of asthma susceptibility will allow disease prediction and risk stratification.

Objective:
We sought to identify asthma susceptibility genes in children.

Methods:
A nested case-control genetic association study of children of Caucasian European ancestry from a birth cohort was conducted. Single nucleotide polymorphisms (SNPs, n = 116,024) were genotyped in pools of DNA samples from cohort children with physician-diagnosed asthma (n = 112) and normal controls (n = 165). A genomic region containing the ATPAF1 gene was found to be significantly associated with asthma. Additional SNPs within this region were genotyped in individual samples from the same children and in 8 independent study populations of Caucasian, African American, Hispanic, or other ancestries. SNPs were also genotyped or imputed in 2 consortia control populations. ATPAF1 expression was measured in bronchial biopsies from asthmatic patients and controls. RESULTS: Asthma was found to be associated with a cluster of SNPs and SNP haplotypes containing the ATPAF1 gene, with 2 SNPs achieving significance at a genome-wide level (P = 2.26 × 10(-5) to 2.2 × 10(-8)). Asthma severity was also found to be associated with SNPs and SNP haplotypes in the primary population. SNP and/or gene-level associations were confirmed in the 4 non-Hispanic populations. Haplotype associations were also confirmed in the non-Hispanic populations (P = .045-.0009). ATPAF1 total RNA expression was significantly (P < .01) higher in bronchial biopsies from asthmatic patients than from controls.

Conclusion:
Genetic variation in the ATPAF1 gene predisposes children of different ancestries to asthma.
asthma, atpaf1, children, gene, genetic, genome-wide association, purinergic, respiratory, single nucleotide polymorphism, snp
0091-6749
753-760.e11
Schauberger, Eric M.
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Ewart, Susan L.
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Arshad, Syed H.
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Huebner, Marianne
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Karmaus, Wifried
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Holloway, John W.
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Friderici, Karen H.
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Ziegler, Julie T.
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Zhang, Hongmei
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Rose-Zerilli, Matthew J.
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Barton, Sheila J.
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Holgate, Stephen T.
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Kilpatrick, Jeffrey R.
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Harley, John B.
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Lajoie-Kadoch, Stephane
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Harley, Isaac
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Hamid, Qutayba
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Kurukulaaratchy, Ramesh J.
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Seibold, Max A.
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Avila, Pedro C.
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Rodriguez-Cintrón, William
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Rodriguez-Santana, Jose R.
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Hu, Donglei
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Gignoux, Christopher
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Romieu, Isabelle
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London, Stephanie
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Burchard, Esteban G.
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Langefeld, Carl D.
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Wills-Karp, Marsha
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Schauberger, Eric M.
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Ewart, Susan L.
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Arshad, Syed H.
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Huebner, Marianne
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Karmaus, Wifried
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Holloway, John W.
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Friderici, Karen H.
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Ziegler, Julie T.
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Zhang, Hongmei
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Rose-Zerilli, Matthew J.
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Barton, Sheila J.
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Holgate, Stephen T.
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Kilpatrick, Jeffrey R.
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Harley, John B.
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Lajoie-Kadoch, Stephane
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Harley, Isaac
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Hamid, Qutayba
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Kurukulaaratchy, Ramesh J.
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Seibold, Max A.
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Avila, Pedro C.
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Rodriguez-Cintrón, William
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Rodriguez-Santana, Jose R.
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Hu, Donglei
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Gignoux, Christopher
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Romieu, Isabelle
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London, Stephanie
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Burchard, Esteban G.
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Langefeld, Carl D.
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Wills-Karp, Marsha
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Schauberger, Eric M., Ewart, Susan L., Arshad, Syed H., Huebner, Marianne, Karmaus, Wifried, Holloway, John W., Friderici, Karen H., Ziegler, Julie T., Zhang, Hongmei, Rose-Zerilli, Matthew J., Barton, Sheila J., Holgate, Stephen T., Kilpatrick, Jeffrey R., Harley, John B., Lajoie-Kadoch, Stephane, Harley, Isaac, Hamid, Qutayba, Kurukulaaratchy, Ramesh J., Seibold, Max A., Avila, Pedro C., Rodriguez-Cintrón, William, Rodriguez-Santana, Jose R., Hu, Donglei, Gignoux, Christopher, Romieu, Isabelle, London, Stephanie, Burchard, Esteban G., Langefeld, Carl D. and Wills-Karp, Marsha (2011) Identification of ATPAF1 as a novel candidate gene for asthma in children. Journal of Allergy and Clinical Immunology, 128 (4), 753-760.e11. (doi:10.1016/j.jaci.2011.04.058). (PMID:21696813)

Record type: Article

Abstract

Background:
Asthma is a common disease of children with a complex genetic origin. Understanding the genetic basis of asthma susceptibility will allow disease prediction and risk stratification.

Objective:
We sought to identify asthma susceptibility genes in children.

Methods:
A nested case-control genetic association study of children of Caucasian European ancestry from a birth cohort was conducted. Single nucleotide polymorphisms (SNPs, n = 116,024) were genotyped in pools of DNA samples from cohort children with physician-diagnosed asthma (n = 112) and normal controls (n = 165). A genomic region containing the ATPAF1 gene was found to be significantly associated with asthma. Additional SNPs within this region were genotyped in individual samples from the same children and in 8 independent study populations of Caucasian, African American, Hispanic, or other ancestries. SNPs were also genotyped or imputed in 2 consortia control populations. ATPAF1 expression was measured in bronchial biopsies from asthmatic patients and controls. RESULTS: Asthma was found to be associated with a cluster of SNPs and SNP haplotypes containing the ATPAF1 gene, with 2 SNPs achieving significance at a genome-wide level (P = 2.26 × 10(-5) to 2.2 × 10(-8)). Asthma severity was also found to be associated with SNPs and SNP haplotypes in the primary population. SNP and/or gene-level associations were confirmed in the 4 non-Hispanic populations. Haplotype associations were also confirmed in the non-Hispanic populations (P = .045-.0009). ATPAF1 total RNA expression was significantly (P < .01) higher in bronchial biopsies from asthmatic patients than from controls.

Conclusion:
Genetic variation in the ATPAF1 gene predisposes children of different ancestries to asthma.

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More information

Published date: October 2011
Keywords: asthma, atpaf1, children, gene, genetic, genome-wide association, purinergic, respiratory, single nucleotide polymorphism, snp
Organisations: Infection Inflammation & Immunity, Human Development & Health

Identifiers

Local EPrints ID: 193743
URI: http://eprints.soton.ac.uk/id/eprint/193743
ISSN: 0091-6749
PURE UUID: 80a86f9d-7e9a-469e-adb9-1c37f2b3ecf1
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for Matthew J. Rose-Zerilli: ORCID iD orcid.org/0000-0002-1064-5350
ORCID for Sheila J. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for Ramesh J. Kurukulaaratchy: ORCID iD orcid.org/0000-0002-1588-2400

Catalogue record

Date deposited: 19 Jul 2011 13:40
Last modified: 15 Mar 2024 03:36

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Contributors

Author: Eric M. Schauberger
Author: Susan L. Ewart
Author: Syed H. Arshad
Author: Marianne Huebner
Author: Wifried Karmaus
Author: Karen H. Friderici
Author: Julie T. Ziegler
Author: Hongmei Zhang
Author: Jeffrey R. Kilpatrick
Author: John B. Harley
Author: Stephane Lajoie-Kadoch
Author: Isaac Harley
Author: Qutayba Hamid
Author: Max A. Seibold
Author: Pedro C. Avila
Author: William Rodriguez-Cintrón
Author: Jose R. Rodriguez-Santana
Author: Donglei Hu
Author: Christopher Gignoux
Author: Isabelle Romieu
Author: Stephanie London
Author: Esteban G. Burchard
Author: Carl D. Langefeld
Author: Marsha Wills-Karp

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