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

作者信息

Ti Yun, Xu Dan, Qin Xiaoning, Hu Yang, Xu Yuru, Zhao Qingzhao, Bu Peili, Li Jingyuan

机构信息

State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.

Department of General Practice, Qilu Hospital of Shandong University, Jinan, China.

出版信息

Sci Rep. 2025 Jan 30;15(1):3834. doi: 10.1038/s41598-025-88375-9.


DOI:10.1038/s41598-025-88375-9
PMID:39885280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11782540/
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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7aa/11782540/fccc5054f4dd/41598_2025_88375_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7aa/11782540/e85ceb7fb4f5/41598_2025_88375_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7aa/11782540/18b7d5c3e34f/41598_2025_88375_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7aa/11782540/fccc5054f4dd/41598_2025_88375_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7aa/11782540/e85ceb7fb4f5/41598_2025_88375_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7aa/11782540/18b7d5c3e34f/41598_2025_88375_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7aa/11782540/fccc5054f4dd/41598_2025_88375_Fig3_HTML.jpg

相似文献

[1]
Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases.

Sci Rep. 2025-1-30

[2]
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[3]
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[4]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Mendelian Randomization as a Tool for Cardiovascular Research: A Review.

JAMA Cardiol. 2024-1-1

[2]
Mendelian randomization for cardiovascular diseases: principles and applications.

Eur Heart J. 2023-12-14

[3]
Mendelian randomization.

Nat Rev Methods Primers. 2022-2-10

[4]
Lipoprotein(a): Role in atherosclerosis and new treatment options.

Biomol Biomed. 2023-7-3

[5]
Elevated Lipoprotein(a) and Risk of Atrial Fibrillation: An Observational and Mendelian Randomization Study.

J Am Coll Cardiol. 2022-4-26

[6]
Transethnic analysis of psoriasis susceptibility in South Asians and Europeans enhances fine-mapping in the MHC and genomewide.

HGG Adv. 2022-1-13

[7]
Whole-exome imputation within UK Biobank powers rare coding variant association and fine-mapping analyses.

Nat Genet. 2021-8

[8]
Interpreting type 1 diabetes risk with genetics and single-cell epigenomics.

Nature. 2021-6

[9]
Treatment and prevention of lipoprotein(a)-mediated cardiovascular disease: the emerging potential of RNA interference therapeutics.

Cardiovasc Res. 2022-3-25

[10]
Residual Cardiovascular Risk at Low LDL: Remnants, Lipoprotein(a), and Inflammation.

Clin Chem. 2021-1-8

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