对银屑病的遗传研究突出表明,银屑病与社会经济地位和情感症状密切相关。

The Journal of investigative dermatology Pub Date : 2024-12-01 Epub Date: 2024-05-18 DOI:10.1016/j.jid.2024.03.043
Anni Heikkilä, Eeva Sliz, Laura Huilaja, Kadri Reis, Priit Palta, Abdelrahman G Elnahas, Anu Reigo, Tõnu Esko, Triin Laisk, Maris Teder-Laving, Kaisa Tasanen, Johannes Kettunen
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引用次数: 0

摘要

银屑病是一种炎症性皮肤病,估计遗传率约为 70%。以往的全基因组关联研究(GWAS)发现了几个银屑病的风险基因位点。为了进一步了解影响该疾病的遗传风险因素,我们在芬兰基因组中进行了发现性全基因组关联研究,随后利用爱沙尼亚生物库和英国生物库的数据进行了复制和荟萃分析;研究样本包括 925 649 人(22 659 例病例和 902 990 例对照),是迄今为止最大的银屑病样本。此外,我们还进行了下游分析,以进一步了解银屑病的跨性状遗传相关性和因果关系。据我们所知,我们报告了 6 个以前从未报告过的风险基因位点,其中大部分基因与活化 B 细胞信号通路的核因子卡巴轻链增强子和整体免疫有关。遗传相关性突显了银屑病与吸烟、较高体重和较低教育水平之间的关系。此外,我们还报告了银屑病与情绪症状之间的因果关系,以及银屑病与较低教育水平之间的双向因果关系。我们的研究结果提供了有关银屑病风险因素的更多知识,这可能有助于未来治疗策略的制定。
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Genetic Study of Psoriasis Highlights its Close Link with Socioeconomic Status and Affective Symptoms.

Psoriasis is an inflammatory skin disease with an estimated heritability of around 70%. Previous GWASs have detected several risk loci for psoriasis. To further improve the understanding of the genetic risk factors impacting the disease, we conducted a discovery GWAS in FinnGen and a subsequent replication and meta-analysis with data from the Estonian Biobank and the UK Biobank; the study sample included 925,649 individuals (22,659 cases and 902,990 controls), the largest sample for psoriasis yet. In addition, we conducted downstream analyses to find out more about psoriasis' cross-trait genetic correlations and causal relationships. We report 6 risk loci, which, to our knowledge, are previously unreported, most of which harbor genes related to NF-κB signaling pathway and overall immunity. Genetic correlations highlight the relationship between psoriasis and smoking, higher body weight, and lower education level. In addition, we report causal relationships between psoriasis and mood symptoms as well as 2-directioned causal relationship between psoriasis and lower education level. Our results provide further knowledge on psoriasis risk factors, which may be useful in the development of future treatment strategies.

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