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Genomic correlation, shared loci, and causal relationship between insomnia and psoriasis: a large-scale genome-wide cross-trait analysis

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Abstract

Psoriasis and insomnia have co-morbidities, however, their common genetic basis is still unclear. We analyzed psoriasis and insomnia with summary statistics from genome-wide association studies. We first quantified overall genetic correlations, then ascertained multiple effector loci and expression-trait associations, and lastly, we analyzed the causal effects between psoriasis and insomnia. A prevalent genetic link between psoriasis and insomnia was found, four pleiotropic loci affecting psoriasis and insomnia were identified, and 154 genes were shared, indicating a genetic link between psoriasis and insomnia. Yet, there is no causal relationship between psoriasis and insomnia by two-sample Mendelian randomization. We discovered a genetic connection between insomnia and psoriasis driven by biological pleiotropy and unrelated to causation. Cross-trait analysis indicates a common genetic basis for psoriasis and insomnia. The results of this study highlight the importance of sleep management in the pathogenesis of psoriasis.

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Data availability

The GWAS data involved in this study are publicly available and the code covered can be obtained from the corresponding author under a reasonable request.

Abbreviations

GWAS:

Genome-wide association study

TWAS:

Transcriptome-wide association study

CPASSOC:

Cross-phenotype association analysis

LD:

Linkage disequilibrium

eQTL:

Expression quantitative trait loci

IVW:

Inverse variance weighting

IVs:

Instrumental variables

MR:

Mendelian randomization

MR-PRESSO:

MR pleiotropy residual sum and outlier

MOG:

Myelin Oligodendrocyte Glycoprotein

MAP2K5:

Mitogen-Activated Protein Kinase Kinase 5

LDSC:

Linkage disequilibrium score regression

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Acknowledgements

We thank the UK Biobank, the FinnGen genomics research project, and other teams, who generously shared the GWAS data.

Funding

This work was supported by National Natural Science Foundation of China (82374313), State key laboratory of Dampness Syndrome of Chinese Medicine Special Fund (SZ2021ZZ29), and Research Fund for Bajian Talents of Guangdong Provincial Hospital of Chinese Medicine (No. BJ2022KY05), the Guangzhou Science and Technology Plan project-Municipal School (College) joint funding project (202201020332, 202201020320).

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QW conceived and presented the idea. QW, YW, and XW processed data and manuscript writing. JZ and LL participated in the acquisition and interpretation of data. JW, YL and LH discussed and reviewed the manuscript critically. All authors contributed to the article and have checked and approved the version of this article as submitted.

Corresponding authors

Correspondence to Jingjing Wu, Yue Lu or Ling Han.

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Our study is based on source open-source data, so there are no ethical issues or other conflicts of interest. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles.

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Wang, Q., Wu, Y., Wang, X. et al. Genomic correlation, shared loci, and causal relationship between insomnia and psoriasis: a large-scale genome-wide cross-trait analysis. Arch Dermatol Res 316, 425 (2024). https://doi.org/10.1007/s00403-024-03178-8

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