RGD Reference Report - Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans. - Rat Genome Database

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Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans.

Authors: Wu, H  Romieu, I  Shi, M  Hancock, DB  Li, H  Sienra-Monge, JJ  Chiu, GY  Xu, H  Del Rio-Navarro, BE  London, SJ 
Citation: Wu H, etal., J Allergy Clin Immunol. 2010 Feb;125(2):321-327.e13. Epub 2009 Nov 11.
RGD ID: 5024945
Pubmed: PMID:19910030   (View Abstract at PubMed)
PMCID: PMC2823974   (View Article at PubMed Central)
DOI: DOI:10.1016/j.jaci.2009.09.007   (Journal Full-text)

BACKGROUND: More than 200 asthma candidate genes have been examined in human association studies or identified with knockout mouse approaches. However, many have not been systematically replicated in human populations, especially those containing a large number of tagging single nucleotide polymorphisms (SNPs). OBJECTIVE: We comprehensively evaluated the association of previously implicated asthma candidate genes with childhood asthma in a Mexico City population. METHODS: From the literature, we identified candidate genes with at least 1 positive report of association with asthma phenotypes in human subjects or implicated in asthma pathogenesis using knockout mouse experiments. We performed a genome-wide association study in 492 asthmatic children aged 5 to 17 years and both parents using the Illumina HumanHap 550v3 BeadChip. Separate candidate gene analyses were performed for 2933 autosomal SNPs in the 237 selected genes by using the log-linear method with a log-additive risk model. RESULTS: Sixty-one of the 237 genes had at least 1 SNP with a P value of less than .05 for association with asthma. The 9 most significant results were observed for rs2241715 in the gene encoding TGF-beta1 (TGFB1; P = 3.3 x 10(-5)), rs13431828 and rs1041973 in the gene encoding IL-1 receptor-like 1 (IL1RL1; P = 2 x 10(-4) and 3.5 x 10(-4)), 5 SNPs in the gene encoding dipeptidyl-peptidase 10 (DPP10; P = 1.6 x 10(-4) to 4.5 x 10(-4)), and rs17599222 in the gene encoding cytoplasmic FMR1 interacting protein 2 (CYFIP2; P = 4.1 x 10(-4)). False discovery rates were less than 0.1 for all 9 SNPs. Multimarker analysis identified TGFB1, IL1RL1, the gene encoding IL-18 receptor 1 (IL18R1), and DPP10 as the genes most significantly associated with asthma. CONCLUSIONS: This comprehensive analysis of literature-based candidate genes suggests that SNPs in several candidate genes, including TGFB1, IL1RL1, IL18R1, and DPP10, might contribute to childhood asthma susceptibility in a Mexican population.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  IAGP 5024945 RGD 
asthma  ISOIL18R1 (Homo sapiens)5024945; 5024945 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il18r1  (interleukin 18 receptor 1)

Genes (Mus musculus)
Il18r1  (interleukin 18 receptor 1)

Genes (Homo sapiens)
IL18R1  (interleukin 18 receptor 1)


Additional Information