Identification of potential therapeutic targets for diffuse idiopathic skeletal hyperostosis via protein quantitative trait locus analysis

doi:10.3877/cma.j.issn.2096-0263.2025.06.004

Abstract

Abstract:

Objective

The proteome represents a key source of therapeutic targets for complex diseases. In this study, we performed a proteome-wide Mendelian randomization (MR) analysis to identify potential protein biomarkers and therapeutic targets for diffuse idiopathic skeletal hyperostosis (DISH).

Methods

Protein quantitative trait loci (pQTL) data were obtained from seven genome-wide association studies (GWASs) on plasma proteomics, encompassing 4,853 circulating proteins. Summary-level genetic associations with DISH were derived from the UK Biobank (9,276 cases and 477,069 controls). Proteome-wide MR and Steiger filtering analyses were conducted to evaluate causal relationships between plasma proteins and DISH risk.

Results

Genetically predicted circulating levels of two proteins, CHAD and TMEM190, were found to be significantly associated with the risk of DISH.

Conclusions

This study identifies two plasma proteins associated with DISH susceptibility and provides novel insights into disease etiology and therapeutic targeting. These findings may contribute to the development of biomarkers and potential drugs for early screening and treatment of DISH.

Key words: Diffuse idiopathic skeletal hyperostosis, Bioinformatics analysis, Mendelian randomization

Guanqi Li, Jiajun Tang, Jieling Liu, Fangmin Wang, Zhiyu Ding, Yi Peng, Weiguo Wang, Jinglei Miao, Shijie Chen, Jinsong Li. Identification of potential therapeutic targets for diffuse idiopathic skeletal hyperostosis via protein quantitative trait locus analysis[J]. Chinese Journal of Geriatric Orthopaedics and Rehabilitation(Electronic Edition), 2025, 11(06): 345-350.

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Figures/Tables 5

References 21

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pQTL研究	蛋白数量	pQTL数量	样本量	平台
Pietzner et al. 2021	4 775	8 328	10 708	SomaLogic
Ferkingstad et al. 2021	4 719	18 084	35 559	SomaLogic
Sun_1 et al. 2018	2 995	1 927	3 301	SomaLogic
Sun_2 et al. 2022	1 463	10 248	54 306	Olink
Suhre et al. 2017	1 124	539	1 000	SomaLogic
Folkersen et al. 2020	90	451	30 000	Olink
Yao et al. 2018	71	16 602	6 861	xMAP

pQTL研究	蛋白数量	pQTL数量	样本量	平台
Pietzner et al. 2021	4 775	8 328	10 708	SomaLogic
Ferkingstad et al. 2021	4 719	18 084	35 559	SomaLogic
Sun_1 et al. 2018	2 995	1 927	3 301	SomaLogic
Sun_2 et al. 2022	1 463	10 248	54 306	Olink
Suhre et al. 2017	1 124	539	1 000	SomaLogic
Folkersen et al. 2020	90	451	30 000	Olink
Yao et al. 2018	71	16 602	6 861	xMAP

蛋白	配体	第1次对接	第2次对接	第3次对接	平均结合能±标准差（kcal/mol）	95%置信区间	预测结合残基（中位数结合能对接预测）
CHAD	多柔比星	-5.35	-5.68	-5.91	-5.65±0.28	[-5.91，-5.36]	GLY244、PHE267
CHAD	索拉非尼	-7.04	-7.11	-7.11	-7.09±0.04	[-7.11，-7.04]	SER48、VAL43

蛋白	配体	第1次对接	第2次对接	第3次对接	平均结合能±标准差（kcal/mol）	95%置信区间	预测结合残基（中位数结合能对接预测）
CHAD	多柔比星	-5.35	-5.68	-5.91	-5.65±0.28	[-5.91，-5.36]	GLY244、PHE267
CHAD	索拉非尼	-7.04	-7.11	-7.11	-7.09±0.04	[-7.11，-7.04]	SER48、VAL43

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