Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves’ Disease and Graves’ Ophthalmopathy
Chenxin Ke,1,* Yuefeng Yu,1,* Jiang Li,1 Yuetian Yu,1 Ying Sun,1 Yuying Wang,1 Bin Wang,1 Yingli Lu,1 Mengjun Tang,2 Ningjian Wang,1 Yi Chen1 1Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine,...
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Dove Medical Press
2025-02-01
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| author | Ke C Yu Y Li J Yu Y Sun Y Wang Y Wang B Lu Y Tang M Wang N Chen Y |
| author_facet | Ke C Yu Y Li J Yu Y Sun Y Wang Y Wang B Lu Y Tang M Wang N Chen Y |
| author_sort | Ke C |
| collection | DOAJ |
| description | Chenxin Ke,1,* Yuefeng Yu,1,* Jiang Li,1 Yuetian Yu,1 Ying Sun,1 Yuying Wang,1 Bin Wang,1 Yingli Lu,1 Mengjun Tang,2 Ningjian Wang,1 Yi Chen1 1Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Orthopedic Department, Taizhou Hospital of Zhejiang Province, Zhejiang University, Taizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Chen, Email chenyi9h@126.com; Ningjian Wang, Email wnj486@126.comBackground: The blood proteome is a major source of biomarkers and therapeutic targets. We aimed to identify the causal proteins and potential targets for Graves’ disease (GD) and Graves’ ophthalmopathy (GO) via systematic genetic analyses.Methods: Genome-wide association studies (GWASs) on the UK Biobank- Pharma Proteomics Project (UKB-PPP) collected 2923 Olink proteins from 54,219 participants. We conducted a proteome-wide Mendelian randomization (MR) study with cis-pQTLs to identify candidate proteins for GD and GO risk. Colocalization analysis and the Heidi test were used to examine whether the identified proteins and diseases shared the same variant. More proteins with potential causal associations were identified in Summary-data-based MR (SMR) analyses using trans-pQTLs. Then, downstream analyses were performed to detect protein interactions, gene function, cell type-specific expression and druggable information.Results: This study genetically predicted levels of 62 plasma proteins were associated with GD risk. Four proteins (CD40, TINAGL1, GMPR and CXCL10) were prioritized with the evidence of sharing the same variants with GD. Specifically, some proteins had potential associations with GD with trans-pQTLs mapping in CD40. The four prioritized protein-coding genes were mainly enriched in the regulation of apoptotic and death processes. In addition, GMPR was associated with both GO and GD in a consistent direction. BTN1A1 and FCRL1 were prioritized as the causal proteins for GO onset and were not associated with GD.Conclusion: By synthesizing proteomic and genetic data, we identified several protein biomarkers for GD, with one linked to both GD and GO and two other protein biomarkers specific to GO onset, which provides valuable insights into the etiology and potential therapeutic targets for the two diseases.Keywords: plasma proteomics, Graves’ disease, Olink, Mendelian randomization |
| format | Article |
| id | doaj-art-615f8e3e194541168206ba7ead0d514b |
| institution | Kabale University |
| issn | 2253-1556 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Dove Medical Press |
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| series | ImmunoTargets and Therapy |
| spelling | doaj-art-615f8e3e194541168206ba7ead0d514b2025-02-06T16:40:25ZengDove Medical PressImmunoTargets and Therapy2253-15562025-02-01Volume 14879899962Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves’ Disease and Graves’ OphthalmopathyKe CYu YLi JYu YSun YWang YWang BLu YTang MWang NChen YChenxin Ke,1,* Yuefeng Yu,1,* Jiang Li,1 Yuetian Yu,1 Ying Sun,1 Yuying Wang,1 Bin Wang,1 Yingli Lu,1 Mengjun Tang,2 Ningjian Wang,1 Yi Chen1 1Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Orthopedic Department, Taizhou Hospital of Zhejiang Province, Zhejiang University, Taizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Chen, Email chenyi9h@126.com; Ningjian Wang, Email wnj486@126.comBackground: The blood proteome is a major source of biomarkers and therapeutic targets. We aimed to identify the causal proteins and potential targets for Graves’ disease (GD) and Graves’ ophthalmopathy (GO) via systematic genetic analyses.Methods: Genome-wide association studies (GWASs) on the UK Biobank- Pharma Proteomics Project (UKB-PPP) collected 2923 Olink proteins from 54,219 participants. We conducted a proteome-wide Mendelian randomization (MR) study with cis-pQTLs to identify candidate proteins for GD and GO risk. Colocalization analysis and the Heidi test were used to examine whether the identified proteins and diseases shared the same variant. More proteins with potential causal associations were identified in Summary-data-based MR (SMR) analyses using trans-pQTLs. Then, downstream analyses were performed to detect protein interactions, gene function, cell type-specific expression and druggable information.Results: This study genetically predicted levels of 62 plasma proteins were associated with GD risk. Four proteins (CD40, TINAGL1, GMPR and CXCL10) were prioritized with the evidence of sharing the same variants with GD. Specifically, some proteins had potential associations with GD with trans-pQTLs mapping in CD40. The four prioritized protein-coding genes were mainly enriched in the regulation of apoptotic and death processes. In addition, GMPR was associated with both GO and GD in a consistent direction. BTN1A1 and FCRL1 were prioritized as the causal proteins for GO onset and were not associated with GD.Conclusion: By synthesizing proteomic and genetic data, we identified several protein biomarkers for GD, with one linked to both GD and GO and two other protein biomarkers specific to GO onset, which provides valuable insights into the etiology and potential therapeutic targets for the two diseases.Keywords: plasma proteomics, Graves’ disease, Olink, Mendelian randomizationhttps://www.dovepress.com/genetic-and-plasma-proteomic-approaches-to-identify-therapeutic-target-peer-reviewed-fulltext-article-ITTplasma proteomicsgraves' diseaseolinkmendelian randomization |
| spellingShingle | Ke C Yu Y Li J Yu Y Sun Y Wang Y Wang B Lu Y Tang M Wang N Chen Y Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves’ Disease and Graves’ Ophthalmopathy ImmunoTargets and Therapy plasma proteomics graves' disease olink mendelian randomization |
| title | Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves’ Disease and Graves’ Ophthalmopathy |
| title_full | Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves’ Disease and Graves’ Ophthalmopathy |
| title_fullStr | Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves’ Disease and Graves’ Ophthalmopathy |
| title_full_unstemmed | Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves’ Disease and Graves’ Ophthalmopathy |
| title_short | Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves’ Disease and Graves’ Ophthalmopathy |
| title_sort | genetic and plasma proteomic approaches to identify therapeutic targets for graves rsquo disease and graves rsquo ophthalmopathy |
| topic | plasma proteomics graves' disease olink mendelian randomization |
| url | https://www.dovepress.com/genetic-and-plasma-proteomic-approaches-to-identify-therapeutic-target-peer-reviewed-fulltext-article-ITT |
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