Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases.

IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Yun Ti, Dan Xu, Xiaoning Qin, Yang Hu, Yuru Xu, Qingzhao Zhao, Peili Bu, Jingyuan Li
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Abstract

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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孟德尔随机化分析不支持脂蛋白(a)与免疫介导的炎症性疾病之间的因果影响。
观察性研究报道了脂蛋白(a) (Lp(a))与免疫介导的炎症性疾病(IMIDs)之间的关联。本研究采用孟德尔随机化(Mendelian Randomization, MR)和多变量随机化(multivariable MR, MVMR)方法探讨脂蛋白(a) [Lp(a)]与免疫介导性炎症性疾病(IMIDs)之间的因果关系。我们基于全基因组关联研究(GWAS) Lp(a)和9种IMIDs的汇总统计数据进行了双向双样本孟德尔随机化分析,特别是乳糜泻(CeD)、克罗恩病(CD)、溃疡性结肠炎(UC)、炎症性肠病(IBD)、多发性硬化症(MS)、牛皮癣(Pso)、类风湿性关节炎(RA)、系统性红斑狼疮(SLE)、1型糖尿病(T1D)和脂质性状的汇总数据。此外,在控制了其他脂质性状,即高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和甘油三酯(TG)后,我们通过MVMR来检验Lp(a)和IMIDs之间关系的独立性。在单变量和多变量MR分析中,我们没有观察到Lp(a)与IMIDs风险之间的因果关系,这对之前的观察性研究提出了挑战。然而,遗传预测的脂质性状HDL-C与1型糖尿病(T1D)的风险增加有关。在观察性研究中,确定观察到的关联的潜在机制需要进一步的研究。
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来源期刊
Scientific Reports
Scientific Reports Natural Science Disciplines-
CiteScore
7.50
自引率
4.30%
发文量
19567
审稿时长
3.9 months
期刊介绍: We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
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