title: Phenotypic and genetic heterogeneity in a genome-wide linkage study of asthma families.
abstract: BACKGROUND
  Asthma is a complex genetic disease with more than 20 genome-wide scans conducted so far. Regions on almost every chromosome have been linked to asthma and several genes have been associated. However, most of these associations are weak and are still awaiting replication.
  
  
  METHODS
  In this study, we conducted a second-stage genome-wide scan with 408 microsatellite markers on 201 asthma-affected sib pair families and defined clinical subgroups to identify phenotype-genotype relations.
  
  
  RESULTS
  The lowest P value for asthma in the total sample was 0.003 on chromosome 11, while several of the clinical subsets reached lower significance levels than in the overall sample. Suggestive evidence for linkage (p = 0.0007) was found for total IgE on chromosomes 1, 7 and again on chromosome 11, as well as for HDM asthma on chromosome 12. Weaker linkage signals could be found on chromosomes 4 and 5 for early onset and HDM, and, newly described, on chromosome 2 for severe asthma and on chromosome 9 for hay fever.
  
  
  CONCLUSIONS
  This phenotypic dissection underlines the importance of detailed clinical characterisations and the extreme genetic heterogeneity of asthma.
authors.affiliation: gsf Institute of Epidemiology, GSF National Research Center for Environment and Health, Neuherberg, germany. janine@ltmueller.de
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.forename: Corinna
authors.initials: C
authors.lastname: Seidel
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Lee
authors.forename: Sabine
authors.initials: S
authors.lastname: Loesgen
authors.forename: Dieter
authors.initials: D
authors.lastname: Bulle
authors.forename: Frank
authors.initials: F
authors.lastname: Friedrichs
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Jellouschek
authors.forename: Julika
authors.initials: J
authors.lastname: Kelber
authors.forename: Angela
authors.initials: A
authors.lastname: Keller
authors.forename: Antje
authors.initials: A
authors.lastname: Schuster
authors.forename: Michael
authors.initials: M
authors.lastname: Silbermann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wahlen
authors.forename: Peter
authors.initials: P
authors.lastname: Wolff
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schlenvoigt
authors.forename: Franz
authors.initials: F
authors.lastname: Rüschendorf
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Wjst
mesh_terms: D017668:Age of Onset; D001249:Asthma / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D010641:Phenotype