Background

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high heritability. Previous genome-wide association studies have identified several loci predisposing to AD. These findings explain approximately 30% of the variance in AD susceptibility, suggesting that further work is required to fully understand the genetic underpinnings.

Objective

We sought to gain additional understanding of the genetic contribution to AD risk by using biobank resources.

Methods

We completed a genome-wide meta-analysis of AD in 796,661 individuals (N_cases = 22,474) from the FinnGen study, the Estonian Biobank, and the UK Biobank. We further performed downstream in silico analyses to characterize the risk variants at the novel loci.

Results

We report 30 loci associating with AD (P < 5 × 10⁻⁸), 5 of which are novel. In 2 of the novel loci, we identified missense mutations with deleterious predictions in desmocollin 1 and serpin family B member 7, genes encoding proteins crucial to epidermal strength and integrity.

Conclusions

These findings elucidate novel genetic pathways involved in AD pathophysiology. The likely involvement of desmocollin 1 and serpin family B member 7 in AD pathogenesis may offer opportunities for the development of novel treatment strategies for AD in the future.

中文翻译：

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联合生物库资源揭示了调节特应性皮炎易感性的新遗传途径

背景

特应性皮炎（AD）是一种常见的慢性炎症性皮肤病，具有很高的遗传力。以前的全基因组关联研究已经确定了几个易患 AD 的基因座。这些发现解释了大约 30% 的 AD 易感性差异，表明需要进一步的工作来充分了解遗传基础。

客观的

我们试图通过使用生物库资源来进一步了解遗传对 AD 风险的贡献。

方法

 我们完成了对来自 FinnGen 研究、爱沙尼亚生物银行和英国生物银行的796,661 名个体（N_例= 22,474）的 AD 的全基因组荟萃分析。我们进一步进行了下游计算机分析，以表征新基因座的风险变异。

结果

我们报告了 30 个与 AD 相关的位点 ( P  < 5 × 10 ^-8 )，其中 5 个是新的。在 2 个新基因座中，我们发现了在去粒蛋白 1 和丝氨酸蛋白酶抑制剂家族 B 成员 7 中具有有害预测的错义突变，这些基因编码对表皮强度和完整性至关重要的蛋白质。

结论

这些发现阐明了涉及 AD 病理生理学的新遗传途径。桥联蛋白 1 和丝氨酸蛋白酶抑制剂家族 B 成员 7 可能参与 AD 发病机制可能为未来开发新的 AD 治疗策略提供机会。