A genome-wide screen on the genetics of atopy in a multiethnic European population reveals a major atopy locus on chromosome 3q21.3.
BACKGROUND
Dissecting complex diseases in underlying distinct traits and studying these for their genetic basis might enhance the power as well as the specificity, of detection of disease genes. These phenotypes are known as intermediate phenotypes.


OBJECTIVE
We were interested in the atopic basis of asthma, and used the sensitization to mite (Dermatophagoides pteronyssinus) allergens as a pathophysiologically important intermediate phenotype.


METHODS
This time we performed a genome-wide scan based on the same already used multiethnic European population consisting of 82 nuclear families with at least two affected siblings. We carried out nonparametric as well as parametric MOD-score analyses based on the genotypes of 603 microsatellite markers.


RESULTS
In comparison with our first genome-wide candidate region search three novel regions additionally appeared to be significant. We obtained significant results for the region 2p12 with a MOD score of 3.35 and for the region 16q21 with a MOD score of 4.18. The most significant result was found for the region 3q21.3 with the same microsatellite marker, which showed significant linkage to atopic dermatitis (AD) in another study with a MOD score of 4.51 and an nonparametric linkage analysis (NPL) of 4.00.


CONCLUSIONS
Our findings indicate that atopy, allergic asthma, allergic rhinitis and AD on the one hand are distinct traits on both the clinical and genetic basis, but on the other hand, our results also underline that these traits are closely related diseases concerning the atopic basis of the traits.
Kurz
T
T
University Children's Hospital, University of Freiburg, Freiburg, Germany.
Altmueller
J
J
Strauch
K
K
Rüschendorf
F
F
Heinzmann
A
A
Moffatt
M F
MF
Cookson
W O C M
WO
Inacio
F
F
Nürnberg
P
P
Stassen
H H
HH
Deichmann
K A
KA
D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000235:genetics; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003876:Dermatitis, Atopic / Q000235:genetics; D005060:Europe; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D015894:Genome, Human; D006801:Humans; D006967:Hypersensitivity / Q000208:ethnology* / Q000235:genetics*; D008126:Lod Score; D018895:Microsatellite Repeats; D010641:Phenotype
D039741:Antigens, Dermatophagoides