A genome-wide association study of hand eczema identifies locus 20q13.33 and reveals genetic overlap with atopic dermatitis

IF 4.8 1区医学 Q2 ALLERGY Contact Dermatitis Pub Date : 2024-06-24 DOI:10.1111/cod.14619

Fieke M. Rosenberg, Peter J. van der Most, Laura Loman, Zoha Kamali, Daan Dittmar, Harold Snieder, Marie L. A. Schuttelaar

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Abstract

Background

Twin studies revealed that genetic effects play a role in hand eczema (HE), but the responsible genetic factors are unknown.

Objectives

To identify and characterise genetic loci associated with HE and to provide insight into the genetic overlap between HE and atopic dermatitis (AD).

Methods

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.

Results

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 (r_g = 0.65), regardless of adjusting for AD (r_g = 0.63).

Conclusions

Locus 20q13.33 is associated with HE, and there is a large genetic overlap between HE and AD.

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手部湿疹的全基因组关联研究确定了 20q13.33 位点，并揭示了与特应性皮炎的遗传重叠。

背景：双生子研究显示，遗传效应在手湿疹（HE）中起着一定作用，但导致手湿疹的遗传因素尚不清楚：目的：确定与手部湿疹相关的遗传位点并描述其特征，同时深入了解手部湿疹与特应性皮炎（AD）之间的遗传重叠：方法：我们使用了来自欧洲人群生命线队列和生物库的问卷调查数据和基因型数据。我们对 HE（2879 例病例和 16 249 例对照）和 AD（1706 例病例和 17 190 例对照）进行了发现性全基因组关联研究（GWAS）。我们在独立的生命线样本中对 HE（1188 例病例和 6431 例对照）和 AD（757 例病例和 6747 例对照）重复了我们的研究结果。我们进行了多项 GWAS 后分析，并对 HE 结果和独立的 AD 数据进行了遗传相关性分析：结果： HE 的两步 GWAS，无论是否对 AD 进行调整，都确定了一个独立的基因位点 20q13.33，该位点很可能是由一些致病单核苷酸多态性驱动的。在 AD 的 GWAS 中，我们复制了 1q21.3 位点（FLG，FLGAS1）上的一个已知的停止增益 rs61816761。我们发现，无论是否对注意力缺失症进行调整（rg = 0.63），都存在很强的遗传相关性（p g = 0.65）：结论：20q13.33位点与HE相关，HE和AD之间存在大量遗传重叠。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Contact Dermatitis 医学-过敏

CiteScore

4.60

自引率

30.90%

发文量

227

审稿时长

4-8 weeks

期刊介绍： Contact Dermatitis is designed primarily as a journal for clinicians who are interested in various aspects of environmental dermatitis. This includes both allergic and irritant (toxic) types of contact dermatitis, occupational (industrial) dermatitis and consumers" dermatitis from such products as cosmetics and toiletries. The journal aims at promoting and maintaining communication among dermatologists, industrial physicians, allergists and clinical immunologists, as well as chemists and research workers involved in industry and the production of consumer goods. Papers are invited on clinical observations, diagnosis and methods of investigation of patients, therapeutic measures, organisation and legislation relating to the control of occupational and consumers".