TY - JOUR
T1 - Identification of ATPAF1 as a novel candidate gene for asthma in children
AU - Schauberger, Eric M.
AU - Ewart, Susan L.
AU - Arshad, Syed H.
AU - Huebner, Marianne
AU - Karmaus, Wilfried
AU - Holloway, John W.
AU - Friderici, Karen H.
AU - Ziegler, Julie T.
AU - Zhang, Hongmei
AU - Rose-Zerilli, Matthew J.
AU - Barton, Sheila J.
AU - Holgate, Stephen T.
AU - Kilpatrick, Jeffrey R.
AU - Harley, John B.
AU - Lajoie-Kadoch, Stephane
AU - Harley, Isaac T.W.
AU - Hamid, Qutayba
AU - Kurukulaaratchy, Ramesh J.
AU - Seibold, Max A.
AU - Avila, Pedro C.
AU - Rodriguez-Cintrón, William
AU - Rodriguez-Santana, Jose R.
AU - Hu, Donglei
AU - Gignoux, Christopher
AU - Romieu, Isabelle
AU - London, Stephanie J.
AU - Burchard, Esteban G.
AU - Langefeld, Carl D.
AU - Wills-Karp, Marsha
N1 - Funding Information:
1998 National Institutes of Health Bethesda E14 The Wellcome Trust Case Control Consortium
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
KW - ATPAF1
KW - Asthma
KW - SNP
KW - children
KW - gene
KW - genetic
KW - genome-wide association
KW - purinergic
KW - respiratory
KW - single nucleotide polymorphism
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U2 - 10.1016/j.jaci.2011.04.058
DO - 10.1016/j.jaci.2011.04.058
M3 - Article
C2 - 21696813
AN - SCOPUS:80053560647
SN - 0091-6749
VL - 128
SP - 753-760.e11
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4
ER -