一项手部湿疹的全基因组关联研究确定了 20q13.33 位置，并揭示了与特应性皮炎的遗传重叠。

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

机构信息

Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

出版信息

Contact Dermatitis. 2024 Sep;91(3):190-202. doi: 10.1111/cod.14619. Epub 2024 Jun 24.

DOI:10.1111/cod.14619

PMID:38924601

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

CONCLUSIONS

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

摘要

背景

双胞胎研究表明，遗传因素在手部湿疹（HE）中起作用，但负责的遗传因素尚不清楚。

目的

确定和描述与 HE 相关的遗传基因座，并深入了解 HE 与特应性皮炎（AD）之间的遗传重叠。

方法

我们使用来自欧洲基于人群的 Lifelines 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 16249 例对照）和 AD（1706 例病例和 17190 例对照）进行了全基因组关联研究（GWAS）。我们在独立的 Lifelines 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）进行了重复验证。我们进行了几次 GWAS 后分析，并对我们的 HE 结果与独立的 AD 数据进行了遗传相关性分析。

结果

无论是否调整 AD，HE 的两步 GWAS 都确定了一个独立的 20q13.33 基因座，该基因座可能由多个因果单核苷酸多态性驱动。对于 AD 的 GWAS，我们复制了已知的 1q21.3 处的停止获得性 rs61816761（FLG，FLGAS1）。我们发现 HE 与 AD 之间存在很强的遗传相关性（p<0.01），无论是否调整 AD（r=0.63）。