Genetically Predicted Association of 91 Circulating Inflammatory Proteins with Multiple Sclerosis: A Mendelian
Xin'ai Li1, Zhiguo Ding1,2,3, Shuo Qi1,2,3
1Department of Thyropathy, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100013, China.
Brain Sciences
|August 29, 2024
Summary
This Mendelian randomization study investigated inflammatory proteins and multiple sclerosis (MS). While CCL25 and CXCL10 showed potential links to increased MS risk, and NRTN to decreased risk, these associations require further validation in larger studies.
Area of Science:
- Immunology
- Genetics
- Neuroscience
Background:
- Multiple sclerosis (MS) is linked to inflammation, but causal relationships between specific circulating inflammatory proteins and MS risk remain unclear.
- Understanding these links is crucial for identifying potential therapeutic targets and biomarkers for MS.
Purpose of the Study:
- To investigate the causal effect of 91 circulating inflammatory proteins on the risk of developing multiple sclerosis (MS) using Mendelian randomization (MR).
- To explore potential novel biomarkers and therapeutic targets for MS based on inflammatory protein associations.
Main Methods:
- A two-sample Mendelian randomization (MR) approach was utilized, analyzing data from a large-scale genome-wide association study (GWAS).
- Inverse-variance-weighted (IVW) analysis was the primary method, fortified by MR Egger, weighted median, simple mode, and weighted mode.
- Sensitivity analyses, including Bonferroni and false discovery rate (FDR) corrections, were performed to ensure robustness and exclude heterogeneity and pleiotropy.
Main Results:
- Forward MR analysis suggested that higher levels of CCL25 and CXCL10 may be associated with an increased risk of MS.
- Conversely, elevated levels of neurturin (NRTN) were associated with a decreased risk of MS.
- Reverse MR analysis did not reveal a causal relationship between MS and the studied inflammatory cytokines, and initial findings did not survive stringent statistical corrections.
Conclusions:
- While certain inflammatory proteins like CCL25, CXCL10, and NRTN show potential associations with MS risk, these links are weak and require further investigation.
- The study highlights the need for larger sample sizes to confirm these findings and their clinical relevance.
- Despite limitations, the research offers insights into the complex interplay between inflammation and MS, suggesting avenues for future biomarker and therapeutic target discovery.
