Genetically supported protein signals and ferroptosis-related cell states in human intervertebral disc degeneration: local pQTL–FinnGen screening integrated with nucleus pulposus single-cell RNA sequencing
4 affiliations
- 1Department of Bone Injury, Qiannan Buyei and Miao Autonomous Prefecture Hospital of Traditional Chinese Medicine, Duyun, Guizhou, China
- 2Department of Orthopedics, The Second People’s Hospital of Kashgar Prefecture, Kashgar, Xinjiang, China
- 3Outpatient Department Physical Examination Center, General Hospital of Western Theater of Chinese People’s Liberation Army, Chengdu, Sichuan, China
- 4Department of Orthopaedics, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Abstract
Background: Intervertebral disc degeneration (IVDD) involves nucleus pulposus (NP) cell dysfunction, inflammatory remodeling, and oxidative stress. Genetic support for circulating protein signals and their cell-type-specific context remains incompletely defined.
Methods: We integrated deCODE cis-pQTL data with FinnGen R12 M13_INTERVERTEB and human NP scRNA-seq (GSE153066). Local MR screening used harmonized variants with Benjamini–Hochberg correction. The scRNA-seq analysis retained 70,622 cells from 16 libraries and used library-level pseudobulk comparisons. A qPCR validation experiment in PMA-differentiated THP-1 cells (ATCC TIB-202) evaluated MST1, SAA1, BPI, and GCLM under an inflammatory condition.
Results: Four multi-SNP signals passed correction: MST1 showed higher endpoint odds (OR = 1.057, q = 4.15 × 10−6), whereas DLK1 (OR = 0.933, q = 0.016), ITIH1 (OR = 0.926, q = 0.016), and SAA1 (OR = 0.927, q = 0.023) showed inverse associations. TP53I3 and BPI remained nominal exploratory signals. TFRC showed a BH-positive single-SNP result (OR = 1.471, q = 0.023). ScRNA-seq resolved eight broad cell populations and demonstrated between-library heterogeneity; nominal macrophage-composition and selected expression differences did not survive within-panel correction. In the qPCR experiment, relative expression was 1.34 for MST1, 0.31 for SAA1, 3.46 for BPI, and 1.70 for GCLM (control = 1.0; n = 4 independent biological replicates/group; all Welch P < 0.001), consistent with the scRNA-seq directions.
Conclusions: The study identifies genetically supported protein signals and ferroptosis-related cellular expression patterns while separating genetic screening from transcriptomic localization. The qPCR experiment provides orthogonal experimental support for selected candidate expression changes in the THP-1 inflammatory model.
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BibTeX
@article{tang2026genetically,
title = {{Genetically supported protein signals and ferroptosis-related cell states in human intervertebral disc degeneration: local pQTL–FinnGen screening integrated with nucleus pulposus single-cell RNA sequencing}},
author = {Guangying Tang and Xinjun Wu and Yongchun Lin and Zhiyu Tang and He Liang},
journal = {Frontiers in Cell and Developmental Biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1944218},
url = {https://doi.org/10.3389/fcell.2026.1944218},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Genetically supported protein signals and ferroptosis-related cell states in human intervertebral disc degeneration: local pQTL–FinnGen screening integrated with nucleus pulposus single-cell RNA sequencing
AU - Guangying Tang
AU - Xinjun Wu
AU - Yongchun Lin
AU - Zhiyu Tang
AU - He Liang
PY - 2026
DA - 2026/10/21
JO - Frontiers in Cell and Developmental Biology
DO - 10.3389/fcell.2026.1944218
UR - https://doi.org/10.3389/fcell.2026.1944218
AB - Background: Intervertebral disc degeneration (IVDD) involves nucleus pulposus (NP) cell dysfunction, inflammatory remodeling, and oxidative stress. Genetic support for circulating protein signals and their cell-type-specific context remains incompletely defined. Methods: We integrated deCODE cis-pQTL data with FinnGen R12 M13_INTERVERTEB and human NP scRNA-seq (GSE153066). Local MR screening used harmonized variants with Benjamini–Hochberg correction. The scRNA-seq analysis retained 70,622 cells from 16 libraries and used library-level pseudobulk comparisons. A qPCR validation experiment in PMA-differentiated THP-1 cells (ATCC TIB-202) evaluated MST1, SAA1, BPI, and GCLM under an inflammatory condition. Results: Four multi-SNP signals passed correction: MST1 showed higher endpoint odds (OR = 1.057, q = 4.15 × 10−6), whereas DLK1 (OR = 0.933, q = 0.016), ITIH1 (OR = 0.926, q = 0.016), and SAA1 (OR = 0.927, q = 0.023) showed inverse associations. TP53I3 and BPI remained nominal exploratory signals. TFRC showed a BH-positive single-SNP result (OR = 1.471, q = 0.023). ScRNA-seq resolved eight broad cell populations and demonstrated between-library heterogeneity; nominal macrophage-composition and selected expression differences did not survive within-panel correction. In the qPCR experiment, relative expression was 1.34 for MST1, 0.31 for SAA1, 3.46 for BPI, and 1.70 for GCLM (control = 1.0; n = 4 independent biological replicates/group; all Welch P < 0.001), consistent with the scRNA-seq directions. Conclusions: The study identifies genetically supported protein signals and ferroptosis-related cellular expression patterns while separating genetic screening from transcriptomic localization. The qPCR experiment provides orthogonal experimental support for selected candidate expression changes in the THP-1 inflammatory model.
SN - 2296-634X
ER -