Genome-wide association study meta-analysis of lichen sclerosus reveals immune pathways and drug repurposing opportunities

https://academic.oup.com/bjd/advance-article-abstract/doi/10.1093/bjd/ljag145/8654695

This is a commentary on a study, it's not available for free, but I'll quote some notable parts. Sorry about the screwed up line breaks, but that's what I get when I copy and paste.

it is remarkable that this issue of the BJD features the

first genome-wide association study (GWAS) meta-analysis of LS,

particularly given that LS cohorts have been accessible in multiple

digital biobanks for almost a decade.1,2 Here, Dand et al. queried

three such biobanks [the UK Biobank, the Trøndelag Health Study

(HUNT) and FinnGen] using International Classification of

Diseases, 10th Edition (ICD-10) code L90.0, combined with self-

reported data in the UK Biobank, and identified 6681 and 970

cases of LS in females and males, respectively, among a cohort of

746,360 research participants.

(...)

In addition to HLA-II genes, statistical and functional fine-

mapping also implicated several genes that contribute to skin

inflammation and autoimmunity, including IL2RB, IL7R, SH2B3

(also known as LNK), ALDH2, CD247, IGFLR1, LINC01123, LRRC43,

MAPKAPK5-AS1, MLXIP, VPS33A, ZBTB32 and KIAA1109. The LS risk

haplotype carrying KIAA1109 also contains IL2 and IL21.

(...)

This important study highlights convergent immune signalling

pathways as central to LS pathogenesis and suggests a clear path

forward for drug repurposing. For example, multiple genes across

loci contribute to interleukin (IL)-2 signalling, supporting prior evi-

dence implicating IL-2 in LS and nominating treatments that target

this pathway.3,4 Together, IL2, IL7R and SH2B3 implicate Janus

kinase/signal transducer and activator of transcription (JAK-STAT)

signalling. Importantly, genetic evidence from this study also pro-

vides mechanistic links to other autoimmune diseases (Table 1),

some of which are well-established LS comorbidities, further sup-

porting shared disease mechanisms. These initial discoveries have

the potential to shift the treatment paradigm from nonspecific

immunosuppression toward treatments that target well-defined

disease pathways. Future Mendelian randomization studies will

help resolve the causal structure of these disease associations and

refine our understanding of drug repurposing opportunities.