Allergic disease trajectories have been modelled using already existing longitudinal data on allergy symptoms and doctor diagnoses from birth up to adolescence. A collaboration with the Swedish BAMSE birth cohort has been established for replication purposes. Seven robust allergic disease trajectories have been identified: “early-transient asthma“, “early-resolving dermatitis,” “mid-persisting dermatitis,” “persisting dermatitis plus rhinitis”, “rhinitis”, “multimorbid” and “intermittently allergic”. Those groups were defined by a distinct risk profile, including associations with early-life determinants such as older siblings, pet exposure or parental history of allergies. Additionally, specific trajectories with early onset and more severe disease courses were associated with polygenic risk scores for the respective allergic diseases and could be described by clinical characteristics, such as a higher food or aeroallergen sensitisation as well as reduced lung function in the multimorbid cluster. This work was published in the Allergy journal.
To identify novel genetic risk variants for atopic dermatitis, more than 40 studies including individuals of European, Japanese, Latino and African ancestry were invited to contribute to a meta-analysis of genome-wide association studies. A total of 81 loci were identified amongst individuals of European ancestry and an additional 10 loci in a multi-ancestry analysis. Comprehensive post-GWAS analyses implicated many genes related to the immune system as potential causal genes at the loci that could serve as potential novel drug targets in the future. These findings were published in Nature Communications.
DNA methylation has been measured in 250 paired samples at ages 6 and 10 years and has been analysed regarding allergic diseases and aeroallergen sensitisation. Six methylation risk scores have been calculated based on effect estimates from previous epigenome-wide association studies on various phenotypes related to allergic disease and their association with aeroallergen sensitisation has been evaluated. All allergy-related methylation risk scores were significantly associated with aeroallergen sensitisation in cross-scectional models, but limited evidence was found for MRS as prospective predictors of sensitisation development. Therefore, three high-dimensional mediation approaches (DACT, HIMA, gHMA) have been applied in a follow-up analysis to test whether altered DNA methylation is a cause or a consequence of aeroallergen sensitisation. Results indicated that depending on the genomic location DNA methylation might be both: a cross-sectional biomarker as well as a potential clinical predictor of disease development. These analyses were published in Clinical Epigenetics and Allergy.
A meta-analysis on the association between early-life respiratory tract infections and the risk of school-age lower lung function and asthma was conducted. In total, 38 cohorts comprising 150,090 mother-child pairs were included in the analyses, which were performed by the Generation R Study Group, the lead institute, in the Netherlands. Upper respiratory tract infections early in life were associated with an increased risk of asthma at school-age whereas lower respiratory tract infections were associated both with an increased asthma risk and lower lung function. The results were published in the European Respiratory Journal.
