Young Researcher

Background: Twin studies revealed that genetic effects play a role in hand eczema (HE), but the responsible genetic factors are unknown.<br/><br/>Objectives: to identify and characterise genetic loci associated with HE and to provide insight into the genetic overlap between HE and atopic dermatitis (AD).<br/><br/>Methods: We used questionnaire-derived and genotype data from Lifelines, a European population-based cohort and biobank study. We performed a discovery genome-wide association study (GWAS) of HE (2879 cases and 16 249 controls) and of AD (1706 cases and 17 190 controls). We replicated our findings in an independent Lifelines sample for HE (1188 cases and 6431 controls) and AD (757 cases and 6747 controls). Furthermore, we conducted several bioinformatic post-GWAS analyses to identify the most causal variants. Next, we performed genetic correlation analyses between our HE results and independent AD data.<br/><br/>Results: The GWAS of HE, regardless of adjusting for AD, identified and replicated one independent locus 20q13.33. The signal at this locus is likely driven by a number of potentially causal variants and their affected genes (TNFRSF6B, RTEL1, LIME1, STMN3, ZGPAT, SLC2A4RG, ARFRP1). For the AD GWAS, we replicated a known stop-gained variant rs61816761 at locus 1q21.3 (FLG, FLGAS1). We found a strong genetic correlation (p &lt; 0.01) between HE and AD (rg = 0.65), regardless of adjusting for AD (rg = 0.63).<br/><br/>Conclusions: Our study identified that locus 20q13.33 is associated with HE, and demonstrated that there is a large genetic overlap between HE and AD.