A Mendelian Randomization Study of Plasma Homocysteine Levels and Cerebrovascular and Neurodegenerative Diseases
Background: Homocysteine (Hcy) is a toxic amino acid and hyperhomocysteinemia (HHcy) was reported to be associated with both cerebrovascular disease and neurodegenerative disease. Our aim was to assess the causal link between plasma Hcy level and cerebrovascular and neurodegenerative diseases throug...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-04-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.653032/full |
| _version_ | 1818927732394819584 |
|---|---|
| author | Weishi Liu Weishi Liu Weishi Liu Luyang Zhang Luyang Zhang Shen Li Shen Li Shen Li Chen Liu Chen Liu Chen Liu Ying Tong Ying Tong Ying Tong Hui Fang Hui Fang Rui Zhang Rui Zhang Bo Song Bo Song Zongping Xia Zongping Xia Zongping Xia Yuming Xu Yuming Xu |
| author_facet | Weishi Liu Weishi Liu Weishi Liu Luyang Zhang Luyang Zhang Shen Li Shen Li Shen Li Chen Liu Chen Liu Chen Liu Ying Tong Ying Tong Ying Tong Hui Fang Hui Fang Rui Zhang Rui Zhang Bo Song Bo Song Zongping Xia Zongping Xia Zongping Xia Yuming Xu Yuming Xu |
| author_sort | Weishi Liu |
| collection | DOAJ |
| description | Background: Homocysteine (Hcy) is a toxic amino acid and hyperhomocysteinemia (HHcy) was reported to be associated with both cerebrovascular disease and neurodegenerative disease. Our aim was to assess the causal link between plasma Hcy level and cerebrovascular and neurodegenerative diseases through a Mendelian randomization (MR) study.Methods: A two-sample MR study was performed to infer the causal link. We extracted the genetic variants (SNPs) associated with plasma Hcy level from a large genome-wide association study (GWAS) meta-analysis. The main MR analysis was performed using the inverse variance-weighted method. Additional analyses were further performed using MR-Egger intercept and Cochran’s Q statistic to detect the heterogeneity or pleiotropy of our findings.Results: Thirteen Hcy-associated SNPs were selected as instrumental variables. The results showed evidence of a causal link between plasma Hcy level and ischemic stroke (IS) caused by small artery occlusion (SAS, OR = 1.329, 95% CI 1.047–1.612, p = 0.048). Meanwhile, there was no evidence of association between plasma Hcy level and other types of IS, transient ischemic attack (TIA), or neurodegenerative disease. The MR-Egger intercept test indicated no evidence of directional pleiotropy. Results of additional MR analysis indicated that blood pressure (BP) and type 2 diabetes mellitus (T2DM) serve as influencers in the association.Conclusion: The MR study found a little causal link between plasma Hcy level and SAS. The link is likely to be influenced by other risk factors like BP and T2DM. |
| first_indexed | 2024-12-20T03:17:41Z |
| format | Article |
| id | doaj.art-773dbc7cbaae464885dd45412dff5b9f |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-20T03:17:41Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-773dbc7cbaae464885dd45412dff5b9f2022-12-21T19:55:18ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-04-011210.3389/fgene.2021.653032653032A Mendelian Randomization Study of Plasma Homocysteine Levels and Cerebrovascular and Neurodegenerative DiseasesWeishi Liu0Weishi Liu1Weishi Liu2Luyang Zhang3Luyang Zhang4Shen Li5Shen Li6Shen Li7Chen Liu8Chen Liu9Chen Liu10Ying Tong11Ying Tong12Ying Tong13Hui Fang14Hui Fang15Rui Zhang16Rui Zhang17Bo Song18Bo Song19Zongping Xia20Zongping Xia21Zongping Xia22Yuming Xu23Yuming Xu24Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaBackground: Homocysteine (Hcy) is a toxic amino acid and hyperhomocysteinemia (HHcy) was reported to be associated with both cerebrovascular disease and neurodegenerative disease. Our aim was to assess the causal link between plasma Hcy level and cerebrovascular and neurodegenerative diseases through a Mendelian randomization (MR) study.Methods: A two-sample MR study was performed to infer the causal link. We extracted the genetic variants (SNPs) associated with plasma Hcy level from a large genome-wide association study (GWAS) meta-analysis. The main MR analysis was performed using the inverse variance-weighted method. Additional analyses were further performed using MR-Egger intercept and Cochran’s Q statistic to detect the heterogeneity or pleiotropy of our findings.Results: Thirteen Hcy-associated SNPs were selected as instrumental variables. The results showed evidence of a causal link between plasma Hcy level and ischemic stroke (IS) caused by small artery occlusion (SAS, OR = 1.329, 95% CI 1.047–1.612, p = 0.048). Meanwhile, there was no evidence of association between plasma Hcy level and other types of IS, transient ischemic attack (TIA), or neurodegenerative disease. The MR-Egger intercept test indicated no evidence of directional pleiotropy. Results of additional MR analysis indicated that blood pressure (BP) and type 2 diabetes mellitus (T2DM) serve as influencers in the association.Conclusion: The MR study found a little causal link between plasma Hcy level and SAS. The link is likely to be influenced by other risk factors like BP and T2DM.https://www.frontiersin.org/articles/10.3389/fgene.2021.653032/fullMendelian randomizationhomocysteinecerebrovascular diseaseneurodegenerative diseasesmall artery occlusionblood pressure |
| spellingShingle | Weishi Liu Weishi Liu Weishi Liu Luyang Zhang Luyang Zhang Shen Li Shen Li Shen Li Chen Liu Chen Liu Chen Liu Ying Tong Ying Tong Ying Tong Hui Fang Hui Fang Rui Zhang Rui Zhang Bo Song Bo Song Zongping Xia Zongping Xia Zongping Xia Yuming Xu Yuming Xu A Mendelian Randomization Study of Plasma Homocysteine Levels and Cerebrovascular and Neurodegenerative Diseases Frontiers in Genetics Mendelian randomization homocysteine cerebrovascular disease neurodegenerative disease small artery occlusion blood pressure |
| title | A Mendelian Randomization Study of Plasma Homocysteine Levels and Cerebrovascular and Neurodegenerative Diseases |
| title_full | A Mendelian Randomization Study of Plasma Homocysteine Levels and Cerebrovascular and Neurodegenerative Diseases |
| title_fullStr | A Mendelian Randomization Study of Plasma Homocysteine Levels and Cerebrovascular and Neurodegenerative Diseases |
| title_full_unstemmed | A Mendelian Randomization Study of Plasma Homocysteine Levels and Cerebrovascular and Neurodegenerative Diseases |
| title_short | A Mendelian Randomization Study of Plasma Homocysteine Levels and Cerebrovascular and Neurodegenerative Diseases |
| title_sort | mendelian randomization study of plasma homocysteine levels and cerebrovascular and neurodegenerative diseases |
| topic | Mendelian randomization homocysteine cerebrovascular disease neurodegenerative disease small artery occlusion blood pressure |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.653032/full |
| work_keys_str_mv | AT weishiliu amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT weishiliu amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT weishiliu amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT luyangzhang amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT luyangzhang amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT shenli amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT shenli amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT shenli amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT chenliu amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT chenliu amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT chenliu amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT yingtong amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT yingtong amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT yingtong amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT huifang amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT huifang amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT ruizhang amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT ruizhang amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT bosong amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT bosong amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT zongpingxia amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT zongpingxia amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT zongpingxia amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT yumingxu amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT yumingxu amendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT weishiliu mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT weishiliu mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT weishiliu mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT luyangzhang mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT luyangzhang mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT shenli mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT shenli mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT shenli mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT chenliu mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT chenliu mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT chenliu mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT yingtong mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT yingtong mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT yingtong mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT huifang mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT huifang mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT ruizhang mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT ruizhang mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT bosong mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT bosong mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT zongpingxia mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT zongpingxia mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT zongpingxia mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT yumingxu mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases AT yumingxu mendelianrandomizationstudyofplasmahomocysteinelevelsandcerebrovascularandneurodegenerativediseases |