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Observational studies have reported an association between lipoprotein(a) (Lp(a)) and immune-mediated inflammatory diseases (IMIDs). This study used Mendelian Randomization (MR) and multivariable MR (MVMR) to explore the causal relationship between lipoprotein(a) [Lp(a)] and immune-mediated inflammatory diseases (IMIDs). We performed a bidirectional two-sample mendelian randomization analyses based on genome-wide association study (GWAS) summary statistics of Lp(a) and nine IMIDs, specifically celiac disease (CeD), Crohn's disease (CD), ulcerative colitis (UC), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis (Pso), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and summary-level data for lipid traits. Furthermore, we performed MVMR to examine the independence of relationship between Lp(a) and IMIDs after controlling other lipid traits, namely high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). We didn't observe a causal association between Lp(a) and the risk of IMIDs in univariable and multivariable MR analysis, challenging previous observational studies. However, genetically predicted lipid traits HDL-C was associated with increased risk of Type 1 diabetes (T1D). The identification of potential mechanisms underlying the observed associations in observational studies necessitates further investigation.
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http://dx.doi.org/10.1038/s41598-025-88375-9 | DOI Listing |
Mol Syst Biol
September 2025
Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
The complex interplay between circulating metabolites and immune responses, which is pivotal to disease pathophysiology, remains poorly understood and understudied in systematic research. Here, we performed a comprehensive analysis of the immune response and circulating metabolome in two Western European cohorts (534 and 324 healthy individuals) and one from sub-Saharan Africa (323 healthy donors). At the metabolic level, our analysis revealed sex-specific differences in the correlation between phosphatidylcholine and cytokine responses following ex vivo stimulation.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Pharmacological modulation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) through dual GIP/GLP-1 receptor agonists, commonly used for diabetes and obesity, shows promise in reducing alcohol consumption. We applied drug-target Mendelian randomization (MR) using genetic variation at these loci to assess their long-term effects on problematic alcohol use (PAU), binge drinking, alcohol misuse classifications, liver health, and other substance use behaviors. Genetic proxies for lowered BMI, modeling the appetite-suppressing and weight-reducing effects of variants in both the GIPR and GLP1R loci ("GIPR/GLP1R"), were linked with reduced binge drinking in the primary (β = -0.
View Article and Find Full Text PDFJ Matern Fetal Neonatal Med
December 2025
Department of Obstetrics and Gynecology, Yuncheng Central Hospital Affiliated to Shanxi Medical University, Yuncheng, China.
Background: Mood swings are associated with an elevated risk of preterm birth. However, the causal relationships between them still remain unclear.
Methods: We performed a two-sample Mendelian randomization (MR) analysis to clarify the association between mood swings and preterm birth.
Int Heart J
September 2025
Department of Cardiovascular Surgery, West China Hospital, Sichuan University.
Although several observational studies have suggested an association between plasma homocysteine (Hcy), vitamin B12, and folate levels and aortic diseases, including aortic dissection (AD), thoracic aortic aneurysm (TAA), and abdominal aortic aneurysm (AAA), the causality remains unclear. The aortic diameter was also included in the analysis. Therefore, this study employed Mendelian randomization (MR) analysis to investigate the effects of plasma Hcy, vitamin B12, and folate levels on aortic diseases.
View Article and Find Full Text PDFBrain Behav Immun
September 2025
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:
Background: The proteome is a valuable resource for pinpointing therapeutic targets. Therefore, we conducted a proteome-wide Mendelian randomization (MR) study aimed at identifying potential protein markers and therapeutic targets for Anti-N-Methyl-D-Aspartate Receptor Encephalitis (NMDAR-E).
Methods: Protein quantitative trait loci (pQTLs) were obtained from seven published genome-wide association studies (GWASs) focusing on the plasma proteome, resulting in summary-level data for 734 circulating protein markers.