Phenotypic and genetic heterogeneity in a genome-wide linkage study of asthma families.
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.
Altmüller
Janine
J
gsf Institute of Epidemiology, GSF National Research Center for Environment and Health, Neuherberg, germany. janine@ltmueller.de
Seidel
Corinna
C
Lee
Young-Ae
YA
Loesgen
Sabine
S
Bulle
Dieter
D
Friedrichs
Frank
F
Jellouschek
Heidemarie
H
Kelber
Julika
J
Keller
Angela
A
Schuster
Antje
A
Silbermann
Michael
M
Wahlen
Wolfgang
W
Wolff
Peter
P
Schlenvoigt
Gerhard
G
Rüschendorf
Franz
F
Nürnberg
Peter
P
Wjst
Matthias
M
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