%0 Journal Article
%T A genome-wide association study of hand eczema identifies locus 20q13.33 and reveals genetic overlap with atopic dermatitis.
%A Rosenberg FM
%A van der Most PJ
%A Loman L
%A Kamali Z
%A Dittmar D
%A Snieder H
%A Schuttelaar MLA
%J Contact Dermatitis
%V 91
%N 3
%D 2024 Sep 24
%M 38924601
%F 6.419
%R 10.1111/cod.14619
%X <B>BACKGROUND: </B>Twin studies revealed that genetic effects play a role in hand eczema (HE), but the responsible genetic factors are unknown.<BR><B>OBJECTIVE: </B>To identify and characterise genetic loci associated with HE and to provide insight into the genetic overlap between HE and atopic dermatitis (AD).<BR><B>METHODS: </B>We used questionnaire-derived and genotype data from the European population-based Lifelines cohort and biobank. 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). We conducted several post-GWAS analyses and performed genetic correlation analyses between our HE results and independent AD data.<BR><B>RESULTS: </B>The two-step GWAS of HE, regardless of adjusting for AD, identified one independent locus 20q13.33, likely driven by a number of causal single-nucleotide polymorphisms. For the AD GWAS, we replicated a known stop-gained rs61816761 at locus 1q21.3 (FLG, FLGAS1). We found a strong genetic correlation (p < 0.01) between HE and AD (rg = 0.65), regardless of adjusting for AD (rg = 0.63).<BR><B>CONCLUSIONS: </B>Locus 20q13.33 is associated with HE, and there is a large genetic overlap between HE and AD.