title: The nuclear factor I/A (NFIA) gene is associated with the asthma plus rhinitis phenotype.
abstract: BACKGROUND
  A previous genome-wide linkage scan in 295 families of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) showed strong evidence of linkage of the 1p31 region to the combined asthma plus allergic rhinitis (AR) phenotype.
  
  
  OBJECTIVE
  Our purpose was to conduct fine-scale mapping of the 1p31 linkage region to identify the genetic variants associated with asthma plus AR.
  
  
  METHODS
  Association analyses with the asthma plus rhinitis phenotype were first conducted in the EGEA family sample using the family-based association method (FBAT) and logistic regression. The test of homogeneity of association between asthma plus AR versus asthma alone or AR alone was also applied. Replication of EGEA findings was sought in French-Canadian and United Kingdom family samples.
  
  
  RESULTS
  We found a significant association between asthma plus rhinitis and a 1p31 genetic variant (P = 2 × 10(-5) for rs12122228, which reached the multiple testing-corrected threshold) in EGEA using FBAT. There was evidence of heterogeneity of association between asthma plus AR versus asthma alone or AR alone (P = .03). A Meta-analysis of FBAT results from EGEA and French-Canadian families improved evidence for both association and heterogeneity (P = 5 × 10(-6) and P = .008, respectively), whereas a meta-analysis of EGEA, French-Canadian, and United Kingdom samples based on logistic regression slightly increased the evidence for heterogeneity.
  
  
  CONCLUSIONS
  The single nucleotide polymorphism specifically associated to asthma plus rhinitis is located in the flanking 5' untranslated region of the nuclear factor I/A (NFIA) gene, a strong candidate gene for asthma and AR.
authors.affiliation: INSERM U946, Genetic Variation and Human Diseases Unit, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France. Electronic address: Marie-Helene.Dizier@inserm.fr.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Dizier
authors.affiliation: INSERM U946, Genetic Variation and Human Diseases Unit, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Margaritte-Jeannin
authors.affiliation: Université du Québec, Chicoutimi, Quebec, Canada.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Madore
authors.affiliation: National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Miriam
authors.initials: M
authors.lastname: Moffatt
authors.affiliation: INSERM U946, Genetic Variation and Human Diseases Unit, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Brossard
authors.affiliation: INSERM U946, Genetic Variation and Human Diseases Unit, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Lavielle
authors.affiliation: INSERM U946, Genetic Variation and Human Diseases Unit, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Sarnowski
authors.affiliation: Centre de l'Asthme et des Allergies, APHP, Hôpital Trousseau, UMPC, Paris, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Just
authors.affiliation: National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: Cookson
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.affiliation: Université du Québec, Chicoutimi, Quebec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Laprise
authors.affiliation: INSERM U946, Genetic Variation and Human Diseases Unit, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bouzigon
authors.affiliation: INSERM U946, Genetic Variation and Human Diseases Unit, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Demenais
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics*; D002170:Canada; D002648:Child; D005260:Female; D005602:France; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D051839:NFI Transcription Factors / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D065631:Rhinitis, Allergic / Q000235:genetics*; D006113:United Kingdom; D055815:Young Adult
chemical_list: D020121:5' Untranslated Regions; D051839:NFI Transcription Factors; C497592:NFIA protein, human
keywords: Positional cloning; association study; asthma; family sample; family-based association study; logistic regression; rhinitis