Lichen planus (LP) is a T-cell-mediated inflammatory disease affecting squamous epithelia in many parts of the body, most often the skin and oral mucosa. Cutaneous LP is usually transient and oral LP (OLP) is most often chronic, so we performed a large-scale genetic and epidemiological study of LP to address whether the oral and non-oral subgroups have shared or distinct underlying pathologies and their overlap with autoimmune disease. Using lifelong records covering diagnoses, procedures, and clinic identity from 473,580 individuals in the FinnGen study, genome-wide association analyses were conducted on carefully constructed subcategories of OLP ( = 3,323) and non-oral LP ( = 4,356) and on the combined group. We identified 15 genome-wide significant associations in FinnGen and an additional 12 when meta-analyzed with UKBB (27 independent associations at 25 distinct genomic locations), most of which are shared between oral and non-oral LP. Many associations coincide with known autoimmune disease loci, consistent with the epidemiologic enrichment of LP with hypothyroidism and other autoimmune diseases. Notably, a third of the FinnGen associations demonstrate significant differences between OLP and non-OLP. We also observed a 13.6-fold risk for tongue cancer and an elevated risk for other oral cancers in OLP, in agreement with earlier reports that connect LP with higher cancer incidence. In addition to a large-scale dissection of LP genetics and comorbidities, our study demonstrates the use of comprehensive, multidimensional health registry data to address outstanding clinical questions and reveal underlying biological mechanisms in common but understudied diseases.

中文翻译：

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口腔和非口腔扁平苔藓表现出遗传异质性以及自身免疫性疾病和口腔癌的不同风险


扁平苔藓 (LP) 是一种 T 细胞介导的炎症性疾病，影响身体许多部位的鳞状上皮，最常见的是皮肤和口腔粘膜。皮肤 LP 通常是暂时性的，而口腔 LP (OLP) 通常是慢性的，因此我们对 LP 进行了大规模的遗传和流行病学研究，以确定口腔和非口腔亚组是否具有共同或不同的潜在病理学及其与自身免疫性疾病的重叠疾病。 FinnGen 研究中使用涵盖 473,580 名个体的诊断、手术和临床身份的终身记录，对精心构建的 OLP (= 3,323) 和非口腔 LP (= 4,356) 子类别以及组合组进行全基因组关联分析。我们在 FinnGen 中发现了 15 个全基因组显着关联，并在使用 UKBB 进行荟萃分析时发现了另外 12 个关联（25 个不同基因组位置的 27 个独立关联），其中大多数在口腔 LP 和非口腔 LP 之间共享。许多关联与已知的自身免疫性疾病位点一致，这与 LP 与甲状腺功能减退症和其他自身免疫性疾病的流行病学富集一致。值得注意的是，三分之一的 FinnGen 协会表明 OLP 和非 OLP 之间存在显着差异。我们还观察到，OLP 患者患舌癌的风险增加了 13.6 倍，其他口腔癌的风险也增加，这与早期将 LP 与较高癌症发病率联系起来的报告一致。除了对 LP 遗传学和合并症进行大规模剖析之外，我们的研究还展示了如何使用全面、多维的健康登记数据来解决突出的临床问题，并揭示常见但尚未充分研究的疾病的潜在生物学机制。