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PreprintCC BYmedRxiv

Multivariate genetic analysis maps shared biology between psoriasis and cardiovascular diseases

  1. 1University of Patras

Abstract

Psoriasis is associated with increased cardiovascular morbidity, but the extent and structure of the shared genetic architecture remain incompletely understood. We integrated large-scale European-ancestry genome-wide summary statistics for psoriasis and seven cardiovascular diseases to quantify genetic overlap, model shared liability and prioritize candidate mechanisms. Psoriasis showed modest genetic correlations with all cardiovascular outcomes, but mixture modelling estimated that more than half of psoriasis-associated non-zero variants were shared with five cardiovascular diseases. Genomic structural equation modelling of a latent psoriasis-CVD factor identified 167 independent risk loci, including 50 not genome-wide significant in any component trait. Multimodal prioritization nominated 473 candidate genes and 90 approved compounds with therapeutic relevance, including shared targets involving PDE4B, GLP1R, KEAP1 and PRDM16. Mediation and Mendelian randomization analyses implicated cardiometabolic traits, although no single trait accounted for more than half of the shared liability. These results prioritize genetic mechanisms and pharmacological hypotheses for psoriasis-associated cardiovascular multimorbidity.

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BibTeX
@misc{antonatos2026multivariate,
  title = {{Multivariate genetic analysis maps shared biology between psoriasis and cardiovascular diseases}},
  author = {C. Antonatos and E. Georgalaki and I. Tzoulaki and Y. Vasilopoulos},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.19.26365878},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.19.26365878v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Multivariate genetic analysis maps shared biology between psoriasis and cardiovascular diseases
AU  - C. Antonatos
AU  - E. Georgalaki
AU  - I. Tzoulaki
AU  - Y. Vasilopoulos
PY  - 2026
DA  - 2026/10/19
PB  - medRxiv
DO  - 10.64898/2026.10.19.26365878
UR  - https://www.medrxiv.org/content/10.64898/2026.10.19.26365878v1
AB  - Psoriasis is associated with increased cardiovascular morbidity, but the extent and structure of the shared genetic architecture remain incompletely understood. We integrated large-scale European-ancestry genome-wide summary statistics for psoriasis and seven cardiovascular diseases to quantify genetic overlap, model shared liability and prioritize candidate mechanisms. Psoriasis showed modest genetic correlations with all cardiovascular outcomes, but mixture modelling estimated that more than half of psoriasis-associated non-zero variants were shared with five cardiovascular diseases. Genomic structural equation modelling of a latent psoriasis-CVD factor identified 167 independent risk loci, including 50 not genome-wide significant in any component trait. Multimodal prioritization nominated 473 candidate genes and 90 approved compounds with therapeutic relevance, including shared targets involving PDE4B, GLP1R, KEAP1 and PRDM16. Mediation and Mendelian randomization analyses implicated cardiometabolic traits, although no single trait accounted for more than half of the shared liability. These results prioritize genetic mechanisms and pharmacological hypotheses for psoriasis-associated cardiovascular multimorbidity.
ER  -