Genetically determined blood pressure, antihypertensive medications, and risk of Alzheimer’s disease: a Mendelian randomization study
Abstract Background Observational studies suggest that the use of antihypertensive medications (AHMs) is associated with a reduced risk of Alzheimer’s disease (AD); however, these findings may be biased by confounding and reverse causality. We aimed to explore the effects of blood pressure (BP) and...
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-021-00782-y |
| _version_ | 1818615538053545984 |
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| author | Ya-Nan Ou Yu-Xiang Yang Xue-Ning Shen Ya-Hui Ma Shi-Dong Chen Qiang Dong Lan Tan Jin-Tai Yu |
| author_facet | Ya-Nan Ou Yu-Xiang Yang Xue-Ning Shen Ya-Hui Ma Shi-Dong Chen Qiang Dong Lan Tan Jin-Tai Yu |
| author_sort | Ya-Nan Ou |
| collection | DOAJ |
| description | Abstract Background Observational studies suggest that the use of antihypertensive medications (AHMs) is associated with a reduced risk of Alzheimer’s disease (AD); however, these findings may be biased by confounding and reverse causality. We aimed to explore the effects of blood pressure (BP) and lowering systolic BP (SBP) via the protein targets of different AHMs on AD through a two-sample Mendelian randomization (MR) approach. Methods Genetic proxies from genome-wide association studies of BP traits and BP-lowering variants in genes encoding AHM targets were extracted. Estimates were calculated by inverse-variance weighted method as the main model. MR Egger regression and leave-one-out analysis were performed to identify potential violations. Results There was limited evidence that genetically predicted SBP/diastolic BP level affected AD risk based on 400/398 single nucleotide polymorphisms (SNPs), respectively (all P > 0.05). Suitable genetic variants for β-blockers (1 SNP), angiotensin receptor blockers (1 SNP), calcium channel blockers (CCBs, 45 SNPs), and thiazide diuretics (5 SNPs) were identified. Genetic proxies for CCB [odds ratio (OR) = 0.959, 95% confidence interval (CI) = 0.941–0.977, P = 3.92 × 10−6] and overall use of AHMs (OR = 0.961, 95% CI = 0.944–0.978, P = 5.74 × 10−6, SNPs = 52) were associated with a lower risk of AD. No notable heterogeneity and directional pleiotropy were identified (all P > 0.05). Additional analyses partly support these results. No single SNP was driving the observed effects. Conclusions This MR analysis found evidence that genetically determined lowering BP was associated with a lower risk of AD and CCB was identified as a promising strategy for AD prevention. |
| first_indexed | 2024-12-16T16:35:30Z |
| format | Article |
| id | doaj.art-48c108a306a64d9b969a8e05e111435d |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-16T16:35:30Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-48c108a306a64d9b969a8e05e111435d2022-12-21T22:24:29ZengBMCAlzheimer’s Research & Therapy1758-91932021-02-011311910.1186/s13195-021-00782-yGenetically determined blood pressure, antihypertensive medications, and risk of Alzheimer’s disease: a Mendelian randomization studyYa-Nan Ou0Yu-Xiang Yang1Xue-Ning Shen2Ya-Hui Ma3Shi-Dong Chen4Qiang Dong5Lan Tan6Jin-Tai Yu7Department of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan UniversityAbstract Background Observational studies suggest that the use of antihypertensive medications (AHMs) is associated with a reduced risk of Alzheimer’s disease (AD); however, these findings may be biased by confounding and reverse causality. We aimed to explore the effects of blood pressure (BP) and lowering systolic BP (SBP) via the protein targets of different AHMs on AD through a two-sample Mendelian randomization (MR) approach. Methods Genetic proxies from genome-wide association studies of BP traits and BP-lowering variants in genes encoding AHM targets were extracted. Estimates were calculated by inverse-variance weighted method as the main model. MR Egger regression and leave-one-out analysis were performed to identify potential violations. Results There was limited evidence that genetically predicted SBP/diastolic BP level affected AD risk based on 400/398 single nucleotide polymorphisms (SNPs), respectively (all P > 0.05). Suitable genetic variants for β-blockers (1 SNP), angiotensin receptor blockers (1 SNP), calcium channel blockers (CCBs, 45 SNPs), and thiazide diuretics (5 SNPs) were identified. Genetic proxies for CCB [odds ratio (OR) = 0.959, 95% confidence interval (CI) = 0.941–0.977, P = 3.92 × 10−6] and overall use of AHMs (OR = 0.961, 95% CI = 0.944–0.978, P = 5.74 × 10−6, SNPs = 52) were associated with a lower risk of AD. No notable heterogeneity and directional pleiotropy were identified (all P > 0.05). Additional analyses partly support these results. No single SNP was driving the observed effects. Conclusions This MR analysis found evidence that genetically determined lowering BP was associated with a lower risk of AD and CCB was identified as a promising strategy for AD prevention.https://doi.org/10.1186/s13195-021-00782-yBlood pressureAntihypertensive medicationsAlzheimer’s diseaseSingle nucleotide polymorphismMendelian randomization |
| spellingShingle | Ya-Nan Ou Yu-Xiang Yang Xue-Ning Shen Ya-Hui Ma Shi-Dong Chen Qiang Dong Lan Tan Jin-Tai Yu Genetically determined blood pressure, antihypertensive medications, and risk of Alzheimer’s disease: a Mendelian randomization study Alzheimer’s Research & Therapy Blood pressure Antihypertensive medications Alzheimer’s disease Single nucleotide polymorphism Mendelian randomization |
| title | Genetically determined blood pressure, antihypertensive medications, and risk of Alzheimer’s disease: a Mendelian randomization study |
| title_full | Genetically determined blood pressure, antihypertensive medications, and risk of Alzheimer’s disease: a Mendelian randomization study |
| title_fullStr | Genetically determined blood pressure, antihypertensive medications, and risk of Alzheimer’s disease: a Mendelian randomization study |
| title_full_unstemmed | Genetically determined blood pressure, antihypertensive medications, and risk of Alzheimer’s disease: a Mendelian randomization study |
| title_short | Genetically determined blood pressure, antihypertensive medications, and risk of Alzheimer’s disease: a Mendelian randomization study |
| title_sort | genetically determined blood pressure antihypertensive medications and risk of alzheimer s disease a mendelian randomization study |
| topic | Blood pressure Antihypertensive medications Alzheimer’s disease Single nucleotide polymorphism Mendelian randomization |
| url | https://doi.org/10.1186/s13195-021-00782-y |
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