Genetic effects play a role in hand eczema (HE), according to population-based twin and candidate gene studies. However, the genetic factors responsible for HE are not fully understood. Therefore, the aim of this study was to identify and characterize genetic loci associated with HE in Lifelines, a Dutch general population-based prospective cohort and biobank study. The primary analysis consisted of 2.789 cases with self-reported HE and 12.316 healthy controls without self-reported HE, eczema, atopic dermatitis (AD) and/or contact allergy. Secondary analyses were performed, including I) a selection with self-reported HE cases and less stringent controls (only no self-reported HE), and II) case-control matching based on age and gender on primary and secondary analyses. Genome-wide association studies (GWAS) using logistic regression analyses, adjusted for age and sex, were performed on all analyses. The secondary analysis with less stringent controls was additionally adjusted for AD. In both the primary and secondary analyses, we found multiple genome-wide significant single nucleotide polymorphisms (SNPs) at locus 20q13.33. The lead SNP (rs8114049) of the primary analysis is an intron variant mapping to RTEL1 and RTEL1-TNFRSF6B genes (p-value = 2.053x10-11). An in-silico look-up revealed that this SNP is in linkage-disequilibrium with variants previously associated with atopic diseases. Our primary analysis also found significant SNPs in nearby genes TNFRSF6B, ZGPAT, SLC2A4RG, ZBTB46, ARFRP1, LIME1 and STMN3. All secondary analyses, with and without adjustment for AD, showed significant SNPs in similar nearby genes. In conclusion, this is the first study that has found an association between locus 20q13.33 and HE, independent of adjustment for AD.

According to population-based twin and candidate gene studies, genetic effects play a role in hand eczema (HE). However, the genetic factors responsible for HE are not known yet. Therefore, the aim of this study was to identify and characterize genetic loci associated with HE by performing a genome-wide association study in Lifelines, a Dutch general population-based prospective cohort and biobank study. Multiple genome-wide significant single nucleotide polymorphisms (SNPs) at locus 20q13.33 were identified, independent of adjustment for atopic dermatitis (AD). The lead SNP (rs8114049) is an intron variant mapping to _RTEL1_ and _RTEL1-TNFRSF6B_genes (p-value = 2.053x10-11). Other significant SNPs were located near _TNFRSF6B, ZGPAT, SLC2A4RG, ZBTB46, ARFRP1, LIME1_ and _STMN3_ genes. The lead SNP is in linkage-disequilibrium with variants previously associated with AD and dyskeratosis congenita. Despite the results that were independent of AD, there was a significant strong positive correlation between HE and AD. In conclusion, this is the first study that has found an association between locus 20q13.33 and HE, independent of AD. We hypothesized that locus 20q13.33 is associated with eczema in general, as some are immune signaling genes that can be linked to HE and AD. Replication studies are required to validate our findings.

ESDR284 - A genome-wide association study of hand eczema in the Dutch general population

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