Two-gene models implicating functional variants in the IL10 and VDR genes as well as in the IL10 and IL1RL1 genes were associated with asthma (p < 0.0002).
The critical function of IL-33/ST2 signaling in allergic inflammation is illustrated by the fact that IL33 and IL1RL1 are among the most highly replicated susceptibility loci for asthma.
We evidenced a new locus in the 16q12 region (near cylindromatosis turban tumor syndrome gene [CYLD]) and confirmed 4 asthma risk regions: 2q12 (IL-1 receptor-like 1 [IL1RL1]), 6p21 (HLA-DQA1), 9p24 (IL33), and 17q12-q21 (zona pellucida binding protein 2 [ZPBP2]-gasdermin A [GSDMA]).
Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.
Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups.
Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups.
However, a variant in IL1RL1 that is in low linkage disequilibrium with that reported previously was associated with asthma risk after accounting for all variants tested (rs10197862, gene wide P = 0.01).
Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.
We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (P(Stage1+Stage2) = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (P(Stage1+Stage2) = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus.