Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases
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...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-88375-9 |
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| author | Yun Ti Dan Xu Xiaoning Qin Yang Hu Yuru Xu Qingzhao Zhao Peili Bu Jingyuan Li |
| author_facet | Yun Ti Dan Xu Xiaoning Qin Yang Hu Yuru Xu Qingzhao Zhao Peili Bu Jingyuan Li |
| author_sort | Yun Ti |
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| description | 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. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-3f42bfdf77614aea82fb6287cb43bff92025-02-02T12:22:48ZengNature PortfolioScientific Reports2045-23222025-01-011511910.1038/s41598-025-88375-9Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseasesYun Ti0Dan Xu1Xiaoning Qin2Yang Hu3Yuru Xu4Qingzhao Zhao5Peili Bu6Jingyuan Li7State 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 UniversityDepartment of General Practice, Qilu Hospital of Shandong UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityAbstract 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.https://doi.org/10.1038/s41598-025-88375-9Lipoprotein(a)Immune-mediated inflammatory diseasesMendelian randomization analysisLipid traitsMultivariable MR analysis |
| spellingShingle | Yun Ti Dan Xu Xiaoning Qin Yang Hu Yuru Xu Qingzhao Zhao Peili Bu Jingyuan Li Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases Scientific Reports Lipoprotein(a) Immune-mediated inflammatory diseases Mendelian randomization analysis Lipid traits Multivariable MR analysis |
| title | Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases |
| title_full | Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases |
| title_fullStr | Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases |
| title_full_unstemmed | Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases |
| title_short | Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases |
| title_sort | mendelian randomization analysis does not support a causal influence between lipoprotein a and immune mediated inflammatory diseases |
| topic | Lipoprotein(a) Immune-mediated inflammatory diseases Mendelian randomization analysis Lipid traits Multivariable MR analysis |
| url | https://doi.org/10.1038/s41598-025-88375-9 |
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