Gene-environment (GxE) interactions are thought to play a role in the pathogenesis of atopic eczema, but specific genes and environmental factors remain to be elucidated. We analysed data from 25 European studies from 7 countries to test for interaction between 24 loci identified by genome-wide association studies and 10 early-life environmental exposures, on atopic eczema as an outcome. Fourteen of the 240 pairwise interactions reached nominal significance (P<0.05) in the discovery analysis (N=25,300), one was nominally significant in replication analysis (N=198,000) and four were nominally significant in the combined meta-analysis of discovery and replication data (N>200,000). Fixed effect meta-analysis and SNPs coded for risk-increasing allele, showed evidence of interaction between older siblings and rs7146581 (TRAF3) ORexposed 0.96 [0.90-1.04] ORunexposed 1.12 [1.04-1.21] Pinteraction=0.0011 and rs10214237 (IL7R) ORexp 1.16 [1.08-1.26] ORunexp 1.01 [0.94-1.09] Pint=0.0074; tobacco smoke exposure in utero interacted with rs16948048 (ZNF652) ORexp 0.99 [0.94-1.04] ORunexp 1.12 [1.02-1.23] Pint=0.018; and dog exposure with rs10214237 (IL7R) ORexp 1.12 [1.07-1.16] ORunexp 0.99 [0.93-1.05] Pint=0.0013. Interactions which have been reported in observational epidemiological studies between FLG null variants and breast feeding, washing, cat exposure, having an older sibling or cigarette smoke exposure were not replicated. These findings demonstrate some evidence for specific GxE interactions which may be important for disease prevention. Adequately powered statistical analyses for GxE are challenging to achieve and, in the absence of even greater sample sizes, complimentary in vitro assessments are ongoing, to assess these interactions as future therapeutic targets.

ESDR074 - Investigation of gene-environment interactions in atopic eczema using data from 200,000 European cohort participants

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.