Oral and non-oral lichen planus show genetic heterogeneity and differential risk for autoimmune disease and oral cancer

FinnGen, Mary Pat Reeve, Mari Vehviläinen, Shuang Luo, Jarmo Ritari, Juha Karjalainen, Javier Gracia-Tabuenca, Juha Mehtonen, Shanmukha Sampath Padmanabhuni, Nikita Kolosov, Mykyta Artomov, Harri Siirtola, Hanna M. Olilla, Daniel Graham, Jukka Partanen, Ramnik J. Xavier, Mark J. Daly, Samuli Ripatti, Tuula Salo, Maria Siponen

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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 (n = 3,323) and non-oral LP (n = 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.

Original languageEnglish
JournalAmerican Journal of Human Genetics
Volume111
Issue number6
Pages (from-to)1047-1060
Number of pages14
ISSN0002-9297
DOIs
Publication statusPublished - 6 Jun 2024
MoE publication typeA1 Journal article-refereed

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Fields of Science

  • autoimmune disease
  • genetics
  • hypothyroidism
  • lichen planus
  • oral cancer
  • oral lichen planus
  • 1184 Genetics, developmental biology, physiology

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