Proteome-wide Mendelian randomization identified potential drug targets for migraine
文献类型：期刊论文
| 作者 | Xiong, Zhonghua4; Zhao, Lei2,3; Mei, Yanliang4; Qiu, Dong4; Li, Xiaoshuang4; Zhang, Peng4; Zhang, Mantian4; Cao, Jin1; Wang, Yonggang4 |
| 刊名 | JOURNAL OF HEADACHE AND PAIN
 |
| 出版日期 | 2024-09-11 |
| 卷号 | 25期号:1页码:14 |
| 关键词 | Drug targets Migraine Mendelian randomization Proteomics |
| ISSN号 | 1129-2369 |
| DOI | 10.1186/s10194-024-01853-9 |
| 通讯作者 | Cao, Jin(caojin@bucm.edu.cn) ; Wang, Yonggang(w100yg@gmail.com) |
| 英文摘要 | Background: Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). Methods: We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein-protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. Results: We identified 35 protein targets for migraine and its subtypes (p < 8.04 x 10(-6)), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets-FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3-that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%). Conclusions: A set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments. |
| 收录类别 | SCI |
| WOS关键词 | MULTIPLE GENETIC-VARIANTS ; INSULIN-RESISTANCE ; METABOLITES ; COMPLEXITY ; PATHWAYS ; INSIGHTS ; DISEASE ; WOMEN ; BIAS |
| 资助项目 | National Natural Science Foundation of China[32170752] ; National Natural Science Foundation of China[91849104] ; National Natural Science Foundation of China[31770800] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:001310585600001 |
| 出版者 | BMC |
| 资助机构 | National Natural Science Foundation of China |
| 源URL | [http://ir.psych.ac.cn/handle/311026/48891]  |
| 专题 | 心理研究所_中国科学院心理健康重点实验室 |
| 通讯作者 | Cao, Jin; Wang, Yonggang |
| 作者单位 | 1.Beijing Univ Chinese Med, Sch Life Sci, 11 North Third Ring Rd East, Beijing 100105, Peoples R China 2.Univ Chinese Acad Sci, Dept Psychol, 16 Lincui Rd, Beijing, Peoples R China 3.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, 16 Lincui Rd, Beijing, Peoples R China 4.Capital Med Univ, Beijing Tiantan Hosp, Headache Ctr, Dept Neurol, Beijing 100070, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xiong, Zhonghua,Zhao, Lei,Mei, Yanliang,et al. Proteome-wide Mendelian randomization identified potential drug targets for migraine[J]. JOURNAL OF HEADACHE AND PAIN,2024,25(1):14. |
| APA | Xiong, Zhonghua.,Zhao, Lei.,Mei, Yanliang.,Qiu, Dong.,Li, Xiaoshuang.,...&Wang, Yonggang.(2024).Proteome-wide Mendelian randomization identified potential drug targets for migraine.JOURNAL OF HEADACHE AND PAIN,25(1),14. |
| MLA | Xiong, Zhonghua,et al."Proteome-wide Mendelian randomization identified potential drug targets for migraine".JOURNAL OF HEADACHE AND PAIN 25.1(2024):14. |
入库方式： OAI收割
来源：心理研究所
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