title: Identification of ATPAF1 as a novel candidate gene for asthma in children.
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.
  
  
  CONCLUSIONS
  Genetic variation in the ATPAF1 gene predisposes children of different ancestries to asthma.
authors.affiliation: Michigan State University, East Lansing, MI, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Schauberger
authors.forename: Susan L
authors.initials: SL
authors.lastname: Ewart
authors.forename: Syed H
authors.initials: SH
authors.lastname: Arshad
authors.forename: Marianne
authors.initials: M
authors.lastname: Huebner
authors.forename: Wilfried
authors.initials: W
authors.lastname: Karmaus
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.forename: Karen H
authors.initials: KH
authors.lastname: Friderici
authors.forename: Julie T
authors.initials: JT
authors.lastname: Ziegler
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rose-Zerilli
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Barton
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Kilpatrick
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
authors.forename: Stephane
authors.initials: S
authors.lastname: Lajoie-Kadoch
authors.forename: Isaac T W
authors.initials: IT
authors.lastname: Harley
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: Ramesh J
authors.initials: RJ
authors.lastname: Kurukulaaratchy
authors.forename: Max A
authors.initials: MA
authors.lastname: Seibold
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.forename: William
authors.initials: W
authors.lastname: Rodriguez-Cintrón
authors.forename: Jose R
authors.initials: JR
authors.lastname: Rodriguez-Santana
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.forename: Christopher
authors.initials: C
authors.lastname: Gignoux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
mesh_terms: D001249:Asthma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D001980:Bronchi / Q000201:enzymology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases; D018832:Molecular Chaperones; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
chemical_list: D018832:Molecular Chaperones; C498318:ATPAF1 protein, human; D025261:Mitochondrial Proton-Translocating ATPases