Multivariable Mendelian Randomization adjusting for heritable confounding analyzes the causal effects of C-reactive protein on multiple diseases

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

Abstract Background C-reactive protein (CRP) is a marker of inflammation associated with autoimmune, cardiovascular, and neuropsychiatric disorders. However, it remains unclear whether CRP causally affects these traits or if observed associations result from reverse causation confounding. Mendelian randomization (MR) uses genetic variants as instrumental variables to estimate causal effects avoid the biases present in observational studies. Prior MR studies have suggested on several traits, including schizophrenia, bipolar disorder, colorectal cancer. may produce biased results factors that confound exposure outcome are heritable, resulting horizontal pleiotropy. This major concern for CRP, because levels increase response caused by wide range heritable conditions. Methods Multivariable (MVMR) can be used eliminate bias confounding when GWAS summary data available confounders. In this study, we use MVMR 12 outcomes prior evidence associational link CRP. We novel computational pipeline identify broad set potential confounders between each trait MRC-IEU OpenGWAS database. compare computationally selected univariable using narrower, literature derived Results find suggests risk-increasing effect coronary artery disease, knee osteoarthritis, rheumatoid arthritis, protective schizophrenia. after adjusting confounders, only arthritis (OR 1.18, 95% CI [1.07,1.31], p=0.0010 GRAPPLE) schizophrenia 0.87, [0.79,0.96], p=0.0038 remain significant. Additionally, disorder at nominal significance level, which not analysis. Conclusion These suggest analyses high confounding, though indeed play role development some diseases, potentially mediated its innate immunity. also high-light automatic confounder selection improve robustness analyses. Key Messages multivariable various diseases proposed phenome-wide Our study did multiple except rheuma-toid highlights an indicator rather than factor disease risk, suggesting previous been

Language: Английский

Association of immunonutritional indicators with all-cause mortality in adult stroke patients

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 28, 2025

The study aimed to evaluate the relationship between immunonutritional indicators such as systemic immune-inflammation index (SII), Naples prognostic score (NPS), nutritional risk (NRI), serum albumin (ALB), total cholesterol (TC) and all-cause mortality in adult stroke patients. Data were obtained from National Health Nutrition Examination Survey (NHANES) databases for 2005-2018. To determine outcomes, participants matched with Death Index records until December 31, 2019. Spearman's correlation analysis random survival forest (RSF) employed assess relationships among NPS, NRI, SII, ALB, TC, most predictive indicator For selected indicator, Kaplan-Meier Cox proportional hazards regression models subsequently utilized their associations included 1076 patients, a median (IQR) age of 67 (56, 77) years. During follow-up months, 372 (weighted 31%) died all causes. Among evaluated, NPS had strongest power curve Log-rank test showed that was higher group (3-4) compared lower (0-2) (P < 0.001). After adjusting multiple potential confounders, model indicated remained an independent predictor (HR = 1.89, 95% CI 1.44-2.47, P As comprehensive evaluation inflammation nutrition, is powerful

Language: Английский