Assessment of bidirectional relationships between brain imaging-derived phenotypes and stroke: a Mendelian randomization study
Abstract Background Stroke is a major cause of mortality and long-term disability worldwide. Whether the associations between brain imaging-derived phenotypes (IDPs) and stroke are causal is uncertain. Methods We performed two-sample bidirectional Mendelian randomization (MR) analyses to explore the...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-023-02982-9 |
| _version_ | 1797769457587716096 |
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| author | Ke Yu Xiao-Feng Chen Jing Guo Sen Wang Xiao-Ting Huang Yan Guo Shan-Shan Dong Tie-Lin Yang |
| author_facet | Ke Yu Xiao-Feng Chen Jing Guo Sen Wang Xiao-Ting Huang Yan Guo Shan-Shan Dong Tie-Lin Yang |
| author_sort | Ke Yu |
| collection | DOAJ |
| description | Abstract Background Stroke is a major cause of mortality and long-term disability worldwide. Whether the associations between brain imaging-derived phenotypes (IDPs) and stroke are causal is uncertain. Methods We performed two-sample bidirectional Mendelian randomization (MR) analyses to explore the causal associations between IDPs and stroke. Summary data of 587 brain IDPs (up to 33,224 individuals) from the UK Biobank and five stroke types (sample size range from 301,663 to 446,696, case number range from 5,386 to 40,585) from the MEGASTROKE consortium were used. Results Forward MR indicated 14 IDPs belong to projection fibers or association fibers were associated with stroke. For example, higher genetically determined mean diffusivity (MD) in the right external capsule was causally associated with an increased risk of small vessel stroke (IVW OR = 2.76, 95% CI 2.07 to 3.68, P = 5.87 × 10−12). Reverse MR indicated that genetically determined higher risk of any ischemic stroke was associated with increased isotropic or free water volume fraction (ISOVF) in body of corpus callosum (IVW β = 0.23, 95% CI 0.14 to 0.33, P = 3.22 × 10−7). This IDP is a commissural fiber and it is not included in the IDPs identified by forward MR. Conclusions We identified 14 IDPs with statistically significant evidence of causal effects on stroke or stroke subtypes. We also identified potential causal effects of stroke on one IDP of commissural fiber. These findings might guide further work toward identifying preventative strategies at the brain imaging levels. |
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| format | Article |
| id | doaj.art-af360e41909546d4ba8c9a999fe0b9d0 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-03-12T21:09:15Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
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| series | BMC Medicine |
| spelling | doaj.art-af360e41909546d4ba8c9a999fe0b9d02023-07-30T11:17:37ZengBMCBMC Medicine1741-70152023-07-0121111010.1186/s12916-023-02982-9Assessment of bidirectional relationships between brain imaging-derived phenotypes and stroke: a Mendelian randomization studyKe Yu0Xiao-Feng Chen1Jing Guo2Sen Wang3Xiao-Ting Huang4Yan Guo5Shan-Shan Dong6Tie-Lin Yang7Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityAbstract Background Stroke is a major cause of mortality and long-term disability worldwide. Whether the associations between brain imaging-derived phenotypes (IDPs) and stroke are causal is uncertain. Methods We performed two-sample bidirectional Mendelian randomization (MR) analyses to explore the causal associations between IDPs and stroke. Summary data of 587 brain IDPs (up to 33,224 individuals) from the UK Biobank and five stroke types (sample size range from 301,663 to 446,696, case number range from 5,386 to 40,585) from the MEGASTROKE consortium were used. Results Forward MR indicated 14 IDPs belong to projection fibers or association fibers were associated with stroke. For example, higher genetically determined mean diffusivity (MD) in the right external capsule was causally associated with an increased risk of small vessel stroke (IVW OR = 2.76, 95% CI 2.07 to 3.68, P = 5.87 × 10−12). Reverse MR indicated that genetically determined higher risk of any ischemic stroke was associated with increased isotropic or free water volume fraction (ISOVF) in body of corpus callosum (IVW β = 0.23, 95% CI 0.14 to 0.33, P = 3.22 × 10−7). This IDP is a commissural fiber and it is not included in the IDPs identified by forward MR. Conclusions We identified 14 IDPs with statistically significant evidence of causal effects on stroke or stroke subtypes. We also identified potential causal effects of stroke on one IDP of commissural fiber. These findings might guide further work toward identifying preventative strategies at the brain imaging levels.https://doi.org/10.1186/s12916-023-02982-9StrokeIDPsCausal associationMendelian randomization |
| spellingShingle | Ke Yu Xiao-Feng Chen Jing Guo Sen Wang Xiao-Ting Huang Yan Guo Shan-Shan Dong Tie-Lin Yang Assessment of bidirectional relationships between brain imaging-derived phenotypes and stroke: a Mendelian randomization study BMC Medicine Stroke IDPs Causal association Mendelian randomization |
| title | Assessment of bidirectional relationships between brain imaging-derived phenotypes and stroke: a Mendelian randomization study |
| title_full | Assessment of bidirectional relationships between brain imaging-derived phenotypes and stroke: a Mendelian randomization study |
| title_fullStr | Assessment of bidirectional relationships between brain imaging-derived phenotypes and stroke: a Mendelian randomization study |
| title_full_unstemmed | Assessment of bidirectional relationships between brain imaging-derived phenotypes and stroke: a Mendelian randomization study |
| title_short | Assessment of bidirectional relationships between brain imaging-derived phenotypes and stroke: a Mendelian randomization study |
| title_sort | assessment of bidirectional relationships between brain imaging derived phenotypes and stroke a mendelian randomization study |
| topic | Stroke IDPs Causal association Mendelian randomization |
| url | https://doi.org/10.1186/s12916-023-02982-9 |
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