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Abstract：
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 (Ncases = 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.
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 (Ncases = 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.
摘要：
背景：特应性皮炎（AD）是一种常见的慢性炎症性皮肤病，具有高遗传度。先前的全基因组关联研究已经确定了几个诱发AD的基因座。这些发现解释了AD易感性中大约30%的变异，这表明需要进一步的工作来充分理解遗传基础。
目的：我们试图通过使用生物样本库资源来获得对AD风险的遗传贡献的更多了解。
方法：我们完成了来自FinnGen研究的796,661名个体（Ncases=22,474）的AD全基因组荟萃分析，爱沙尼亚生物银行,和英国生物银行。我们进一步进行了下游计算机模拟分析以表征新基因座处的风险变体。
结果：我们报告了30个与AD相关的基因座（P<5×10-8），五是小说。在2的小说基因座中，我们在桥粒蛋白1和serpin家族B成员7中发现了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。Desmocollin1和serpin家族B成员7可能参与AD发病机制，可能为将来开发新的AD治疗策略提供机会。
目的：我们试图通过使用生物样本库资源来获得对AD风险的遗传贡献的更多了解。
方法：我们完成了来自FinnGen研究的796,661名个体（Ncases=22,474）的AD全基因组荟萃分析，爱沙尼亚生物银行,和英国生物银行。我们进一步进行了下游计算机模拟分析以表征新基因座处的风险变体。
结果：我们报告了30个与AD相关的基因座（P<5×10-8），五是小说。在2的小说基因座中，我们在桥粒蛋白1和serpin家族B成员7中发现了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。Desmocollin1和serpin家族B成员7可能参与AD发病机制，可能为将来开发新的AD治疗策略提供机会。
