exploring-targets-for-heart-failure-using-mendelian-randomization

Exploring Targets for Heart Failure Using Mendelian Randomization, Colocalization, Summary Data-based Mendelian Randomization, and Drug Prediction

Heart failure (HF) is a prevalent cardiovascular disease that significantly impairs quality of life in its advanced stages. Despite a variety of current ...

The First Affiliated Hospital of Chongqing Medical University

Rheumatoid arthritis (RA) is a common autoimmune disease. Tuberous sclerosis complex(TSC) is a rare autosomal dominant disorder. We report a case of RA with TSC. The patient was a 46-year-old woman with polyarthritis and cough symptoms, rheumatoid arthritis associated interstitial lung disease (RA-ILD) was initially considered, and after more than 3 months of anti-rheumatic treatment, the patient still had cough, and further examination revealed that the patient had lymphangioleiomyomatosis in the lungs, hepatic and renal angiomyolipomas, multiple subependymal nodules, Vertebral osteosclerotic nodules, as well as facial angiofibromas and periungual fibroma, RA was finally diagnosed with TSC, and everolimus 10mg qd was added to anti-rheumatic therapy for 1 month, and the patient's cough symptoms were relieved.

A case report and review of rheumatoid arthritis co-occurring with tuberous sclerosis complex, a rare occurrence.

 Chronic kidney disease (CKD) impacts millions of individuals annually. Current research suggests that immune factors played a significant role in CKD. However, the potential causal relationship between them remains unclear.  We conducted a comprehensive Mendelian randomization (MR) analysis to assess the potential causal association between 731 immune cells and CKD. Sensitivity analysis was performed to test for heterogeneity and horizontal pleiotropy, including the Cochran Q test, leave-one-out test, MR-Egger intercept analysis, and MR-PRESSO test. The bidirectional MR was utilized to investigate the bidirectional relationship between the immune cells and CKD. Multivariable MR was also conducted to mitigate confounding among immune cells. The colocalization analysis was performed to find the key genes of immune cells. We used the Summary data-based MR (SMR) analysis to generate effect estimates between the cis-eQTL and immune cells. The heterogeneity in dependent instruments (HEIDIs) test was used to test the heterogeneity between dependent instrumental variables.  We identified 14 potential pathogenic factors and six potential protective factors through the univariable MR. Moreover, we did not find reverse causation by using the bidirectional MR. We finally identified one risk factor and two protective factors after multivariate MR adjustment for effects between immune cells. CD28 on CD28 CD45RA CD8 T cell could increase the risk of CKD (Pval: 0.033, OR: 1.112, 95% CI: 1.009-1.227). CD11c on myeloid dendritic cell (DC) could decrease the risk of CKD (Pval: 0.02, OR: 0.854, 95% CI: 0.748-0.975). CD45RA on naive CD4 T cell could decrease the risk of CKD (Pval: 0.026, OR: 0.918, 95% CI: 0.852-0.990). Importantly, we observed no evidence of heterogeneity and pleiotropy, signifying the robustness of our results.  (PPH4.abf = 0.999, P_SMR: <0.001, P_HIEDI: 0.132) and  (PPH4.abf = 0.990, P_SMR: <0.001, P_HIEDI: 0.141) shared the same variant with CD28 on CD28 CD45RA CD8 T cell.  (PPH4.abf = 0.992, P_SMR: <0.001, P_HIEDI: 0.215) shared the same variant with CD11c on myeloid DC.  MR identified a potential correlation between CKD and immune cells. Colocalization and SMR found the key genes of immune cells. Our findings offer insights into the prevention and management of CKD. However, further investigation is required to elucidate the precise mechanisms underlying this relationship.

Article	Year
A case report and review of rheumatoid arthritis co-occurring with tuberous sclerosis complex, a rare occurrence. Frontiers in immunology\| PubMed ID: 39391300	2024
Exploring the Relationship Between Immune Cells and Chronic Kidney Disease by Mendelian Randomization, Colocalization Analysis, and SMR. Mediators of inflammation\| PubMed ID: 40270514	2025

Huiling Zhu

Biography

JoVE Journal Publications

Other Publications