Association and interaction analyses of eight genes under asthma linkage peaks.
BACKGROUND
Linkage studies have implicated the 2q33, 9p21, 11q13 and 20q13 regions in the regulation of allergic disease. The aim of this study was to test genetic variants in candidate genes from these regions for association with specific asthma traits.


METHODS
Ninety-five single nucleotide polymorphisms (SNP) located in eight genes (CD28, CTLA4, ICOS, ADAM23, ADAMTSL1, MS4A2, CDH26 and HRH3) were genotyped in >5000 individuals from Australian (n = 1162), Dutch (n = 99) and Danish (n = 303) families. Traits tested included doctor-diagnosed asthma, atopy, airway obstruction, total serum immunoglobulin (Ig) E levels and eosinophilia. Association was tested using both multivariate and univariate methods, with gene-wide thresholds for significance determined through simulation. Gene-by-gene and gene-by-environment analyses were also performed.


RESULTS
There was no overall evidence for association with seven of the eight genes tested when considering all genetic variation assayed in each gene. The exception was MS4A2 on chromosome 11q13, which showed weak evidence for association with IgE (gene-wide P < 0.05, rs502581). There were no significant gene-by-gene or gene-by-environment interaction effects after accounting for the number of tests performed.


CONCLUSIONS
The individual variants genotyped in the 2q33, 9p21 and 20q13 regions do not explain a large fraction of the variation in the quantitative traits tested or have a major impact on asthma or atopy risk. Our results are consistent with a weak effect of MS4A2 polymorphisms on the variation of total IgE levels.
Ferreira
M A R
MA
Queensland Institute of Medical Research, Brisbane, Australia.
Zhao
Z Z
ZZ
Thomsen
S F
SF
James
M
M
Evans
D M
DM
Postmus
P E
PE
Kyvik
K O
KO
Backer
V
V
Boomsma
D I
DI
Martin
N G
NG
Montgomery
G W
GW
Duffy
D L
DL
D001249:Asthma / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004843:Epistasis, Genetic; D005796:Genes; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood; D011110:Polymorphism, Genetic; D017455:Receptors, IgE / Q000235:genetics
C502447:MS4A2 protein, human; D017455:Receptors, IgE; D007073:Immunoglobulin E