Journal of translational medicineJan 23, 2025

Combined molecular analyses reveal new possible causes of psoriasis

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 29, 2026

Abstract

Significant causal associations were identified between DNA methylation, gene expression, protein levels, and psoriasis risk.

Two pathways involving the long non-coding RNA RP11-977G19.11 and apolipoprotein F (APOF) were discovered.
Methylation at sites cg26804944 and cg02705573 was negatively associated with RP11-977G19.11 expression.
Reduced RP11-977G19.11 expression was linked to increased APOF levels, which were positively associated with a higher risk of psoriasis.
Methylation at sites cg00172967, cg00294382, and cg24773560 was positively associated with RP11-977G19.11 expression.
Elevated RP11-977G19.11 expression was associated with decreased APOF levels, which may reduce the risk of psoriasis.
Colocalization analysis highlighted APOF as a key protein in psoriasis pathogenesis.

Simplified

BACKGROUND: To elucidate the genetic and molecular mechanisms underlying psoriasis by employing an integrative multi-omics approach, using summary-data-based (SMR) to infer causal relationships among DNA methylation, gene expression, and protein levels in relation to psoriasis risk.

METHODS: We conducted SMR analyses integrating genome-wide association study (GWAS) summary statistics with methylation (mQTL), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data. Publicly available datasets were utilized, including psoriasis GWAS data from the European Molecular Biology Laboratory-European Bioinformatics Institute and the UK Biobank. Heterogeneity in dependent instruments (HEIDI) test and colocalization analyses were performed to identify shared causal variants, and multi-omics integration was employed to construct potential regulatory pathways.

RESULTS: Our analyses identified significant causal associations between DNA methylation, gene expression, protein abundance, and psoriasis risk. We discovered two pathways involving the long non-coding RNA RP11-977G19.11 and apolipoprotein F (APOF). Methylation at sites cg26804944 and cg02705573 was negatively associated with RP11-977G19.11 expression. Reduced expression of RP11-977G19.11 was linked to increased APOF levels, which were positively associated with a higher risk of psoriasis. Methylation at sites cg00172967, cg00294382, and cg24773560 was positively associated with RP11-977G19.11 expression. Elevated expression of RP11-977G19.11 was associated with decreased APOF levels, reducing the risk of psoriasis. Colocalization analysis highlighted APOF as a key protein in psoriasis pathogenesis. Validation using skin tissue, EBV-transformed lymphocytes data and inflammation-related protein panels confirmed the associations of RP11-977G19.11 and APOF with psoriasis.

CONCLUSIONS: Our multi-omics analysis provides preliminary evidence for potential molecular mechanisms in psoriasis pathogenesis. Through the integration of GWAS and molecular QTL data, we identify candidate pathways that may be relevant to disease biology. While these findings require extensive experimental validation, they offer a framework for future investigations into the molecular basis of psoriasis.

Key numbers

0.753

Causal Association Odds Ratio (cg26804944)

Methylation at cg26804944 associated with reduced expression of RP11-977G19.11

1.029

Causal Association Odds Ratio (APOF)

APOF levels positively associated with psoriasis risk

5,459 cases and 324,074 controls

Psoriasis Cohort Size

Cohort data from EMBL-EBI for psoriasis analysis

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Combined molecular analyses reveal new possible causes of psoriasis

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