Elke Kurz-Milcke, Gerd Gigerenzer, Laura Martignon
Transparency in risk communication: graphical and analog tools
Annals of the New York Academy of Sciences
many genes associated asthma explain fraction heritability genomewide association studies gwass used broad definition doctordiagnosed asthma thereby diluting genetic signals considering asthma heterogeneity objective study identify genetic associates childhood wheezing phenotypes conducted novel multivariate gwas metaanalysis wheezing phenotypes jointly derived using unbiased analysis data collected birth 18 years 9568 individuals five uk birth cohorts fortyfour independent snps associated earlyonset persistent 25 preschool remitting 33 midchildhood remitting 32 lateonset wheeze identified novel locus chr9q2113 close annexin 1 anxa1 p67 109 associated exclusively earlyonset persistent wheeze identified rs75260654 likely causative single nucleotide polymorphism snp using promoter capture hic loops showed risk allele confers reduction anxa1 expression finally murine model house dust mite hdminduced allergic airway disease demonstrated anxa1 protein expression increased anxa1 mrna significantly induced lung tissue following hdm exposure using anxa1 deficient mice showed loss anxa1 results heightened airway hyperreactivity th2 inflammation upon allergen challenge targeting pathway persistent disease may represent exciting therapeutic prospect uk medical research council programme grant mrs0253401 wellcome trust strategic award 10881815z provided funding study