Replication of genetic association studies in asthma and related phenotypes.
In asthma genetics, the association of highly replicated susceptibility genes lacks consistency across populations. To identify genuine associations, we investigated the reproducibility of the 23 most promising asthma and asthma-related candidate genes in a moderately sized sample from the Japanese population. We compared the frequency of 33 polymorphisms in unrelated cases and controls and tested for their association with asthma, atopy and serum total IgE levels using allele frequency, codominant, dominant and recessive genotype models. On the basis of the consistency of our findings with previous meta-analyses and large replication studies, IL13, TNF, ADAM33, IL4RA and TBXA2R might represent common major asthma and asthma-related trait genes. Individual gene assessment was extended to the interactions between two polymorphisms using our original method. Interactions between TBXA2R and ADAM33, and IL4RA and C3 were suggested to increase the risk for childhood and all asthma (adult and childhood asthma combined). The confirmation of previously reported associations between gene polymorphisms and phenotypes was problematic when as few as several hundred samples per group were used. Stratification of the subjects by environmental factors or other confounding factors may be necessary to improve the sensitivity and reliability of association results.
Undarmaa
Siizkhuu
S
Department of Public Health, Graduate School of Medicine, Chiba University, Chiba, Japan.
Mashimo
Yoichi
Y
Hattori
Satoshi
S
Shimojo
Naoki
N
Fujita
Kimie
K
Miyatake
Akihiko
A
Doi
Satoru
S
Kohno
Yoichi
Y
Okamoto
Yoshitaka
Y
Hirota
Tomomitsu
T
Tamari
Mayumi
M
Hata
Akira
A
Suzuki
Yoichi
Y
D000328:Adult; D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D004777:Environment; D005260:Female; D005796:Genes; D056726:Genetic Association Studies; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic