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. 2011 Jul 31;43(9):893-6.
doi: 10.1038/ng.887.

Genome-wide Association Study Identifies Three New Susceptibility Loci for Adult Asthma in the Japanese Population

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Genome-wide Association Study Identifies Three New Susceptibility Loci for Adult Asthma in the Japanese Population

Tomomitsu Hirota et al. Nat Genet. .
Free PMC article

Abstract

Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10(-12)), a locus on chromosome 10p14 (P = 1.79 × 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.

Figures

Figure 1
Figure 1
Case-control association results and LD map of the MHC region. The blue plots show the -log10 of Cochrane-Armitage trend P values for association results of the GWAS. The LD maps based on D′ were drawn using the genotype data of all cases and controls in the GWAS. Red dotted line, rs404860; blue dotted line, rs8192565; black dotted lines, locations of the SNPs giving significant signals for lung function (rs2070600), FEV1/FVC, in the GWAS and for bronchial asthma in a large-scale, consortium-based GWAS (rs9273349/rs1063355). rs1063355 is absolute LD with rs9273349 (r2 = 1) in the HapMap JPT and CEU populations. Blue arrows indicate the locations of genes. LD among the SNPs is shown in supplementary Table 4.
Figure 2
Figure 2
Case-control association results and LD maps of the four candidate regions. (a-d) P value plot, genomic structures and LD maps of chromosomes 5q22 (a), 10p14 (b), 12q13 (c) and 4q31 (d). The blue plots show the -log10 of Cochrane-Armitage trend P values for association results of the GWAS. The LD maps based on D′ were drawn using the genotype data of all cases and controls in the GWAS. Black and red dotted lines indicate the ranges of the susceptible regions and positions of marker SNPs, respectively. Blue arrows indicate the locations of genes.

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