Shared genetic basis and spatial cellular atlas of psoriasis and metabolic syndrome
4 affiliations
- 1Qionglai Hospital of Traditional Chinese Medicine, Chengdu, China
- 2Faculty of Chinese Medicine, Macau University of Science and Technology, MacauChina
- 3Sichuan Academy of Chinese Medicine Sciences, Chengdu, China
- 4Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, China
Abstract
Background: Psoriasis (PS) and metabolic syndrome (MetS) frequently co-occur. Characterizing their shared genetic architecture and spatially enriched cellular populations may clarify the context of their co-occurrence and generate hypotheses for functional validation. Methods: We integrated genome-wide association study (GWAS) summary statistics for PS, MetS, and five related components with spatially resolved single-cell transcriptomic data. Global and local genetic correlations were assessed using linkage disequilibrium score regression, genetic covariance analysis, high-definition likelihood, and local analysis of variant association. A bivariate causal mixture model quantified polygenic overlap. Conditional/conjunctional false discovery rate and composite-null pleiotropy analyses identified shared susceptibility loci. Finally, gsMap evaluated trait-associated enrichment across annotated embryonic tissues at single-cell resolution. Results: Genetic approaches identified significant genome-wide correlations and polygenic sharing between PS, MetS, and its components. Local and cross-trait analyses identified region-specific signals and cross-validated shared loci. gsMap revealed trait-specific tissue enrichment. PS showed the strongest enrichment in the epidermis (pCauchy = 1.0573 × 10 − ⁴), adipose tissue (pCauchy = 1.5366 × 10 − ⁴), and liver (pCauchy = 1.0167 × 10 − ³). Across MetS, FBG, HDL-C, hypertension, and TG, enriched regions mainly involved the liver, adipose tissue, and epidermis. WC enrichment was predominantly observed in adipose tissue (pCauchy = 1.7823 × 10 − ⁴), with no significant liver or epidermal enrichment. Conclusion: Integrating GWAS with single-cell transcriptomic and spatial information characterized shared genetic architecture between PS and MetS-related phenotypes and their spatial enrichment patterns. These findings provide a framework for generating testable hypotheses about comorbidity biology and guiding future functional and clinical validation.
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BibTeX
@article{liu2026shared,
title = {{Shared genetic basis and spatial cellular atlas of psoriasis and metabolic syndrome}},
author = {Guo Liu and Fengjuan Gong and Guanhu Yang and Yu Li and Yanjiao Ji and Xinyue Chen and Chao Wang and Qinghua Luo},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0358472},
url = {https://doi.org/10.1371/journal.pone.0358472},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Shared genetic basis and spatial cellular atlas of psoriasis and metabolic syndrome
AU - Guo Liu
AU - Fengjuan Gong
AU - Guanhu Yang
AU - Yu Li
AU - Yanjiao Ji
AU - Xinyue Chen
AU - Chao Wang
AU - Qinghua Luo
PY - 2026
DA - 2026/09/15
JO - PLOS One
DO - 10.1371/journal.pone.0358472
UR - https://doi.org/10.1371/journal.pone.0358472
AB - Background: Psoriasis (PS) and metabolic syndrome (MetS) frequently co-occur. Characterizing their shared genetic architecture and spatially enriched cellular populations may clarify the context of their co-occurrence and generate hypotheses for functional validation. Methods: We integrated genome-wide association study (GWAS) summary statistics for PS, MetS, and five related components with spatially resolved single-cell transcriptomic data. Global and local genetic correlations were assessed using linkage disequilibrium score regression, genetic covariance analysis, high-definition likelihood, and local analysis of variant association. A bivariate causal mixture model quantified polygenic overlap. Conditional/conjunctional false discovery rate and composite-null pleiotropy analyses identified shared susceptibility loci. Finally, gsMap evaluated trait-associated enrichment across annotated embryonic tissues at single-cell resolution. Results: Genetic approaches identified significant genome-wide correlations and polygenic sharing between PS, MetS, and its components. Local and cross-trait analyses identified region-specific signals and cross-validated shared loci. gsMap revealed trait-specific tissue enrichment. PS showed the strongest enrichment in the epidermis (pCauchy = 1.0573 × 10 − ⁴), adipose tissue (pCauchy = 1.5366 × 10 − ⁴), and liver (pCauchy = 1.0167 × 10 − ³). Across MetS, FBG, HDL-C, hypertension, and TG, enriched regions mainly involved the liver, adipose tissue, and epidermis. WC enrichment was predominantly observed in adipose tissue (pCauchy = 1.7823 × 10 − ⁴), with no significant liver or epidermal enrichment. Conclusion: Integrating GWAS with single-cell transcriptomic and spatial information characterized shared genetic architecture between PS and MetS-related phenotypes and their spatial enrichment patterns. These findings provide a framework for generating testable hypotheses about comorbidity biology and guiding future functional and clinical validation.
SN - 1932-6203
ER -