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Cited by 14Amyotrophic Lateral Sclerosis ResearchGenetic Associations and EpidemiologyBlood Pressure and Hypertension Studies

Assessing the role of blood pressure in amyotrophic lateral sclerosis: a Mendelian randomization study

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Xia, Kailin, Zhang, Linjing, Tang, Lu, Huang, Tao, Fan, Dongsheng·2022·Orphanet Journal of Rare Diseases
DOI 10.1186/s13023-022-02212-0PMC PMC8848798

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Abstract

Background: Observational studies have suggested a close but controversial relationship between blood pressure (BP) and amyotrophic lateral sclerosis (ALS). It remains unclear whether this association is causal. The authors employed a bidirectional two-sample Mendelian randomization (MR) approach to evaluate the causal relationship between BP and ALS. Genetic proxies for systolic blood pressure (SBP), diastolic blood pressure (DBP), antihypertensive drugs (AHDs), ALS, and their corresponding genome-wide association study (GWAS) summary datasets were obtained from the most recent studies with the largest sample sizes. The inverse variance weighted (IVW) method was adopted as the main approach to examine the effect of BP on ALS and four other MR methods were used for sensitivity analyses. To exclude the interference between SBP and DBP, a multivariable MR approach was used. Results: We found that genetically determined increased DBP was a protective factor for ALS (OR = 0.978, 95% CI 0.960–0.996, P = 0.017) and that increased SBP was an independent risk factor for ALS (OR = 1.014, 95% CI 1.003–1.025, P = 0.015), which is supported by sensitivity analyses. The use of calcium channel blocker (CCB) showed a causal relationship with ALS (OR = 0.985, 95% CI 0.971–1.000, P = 0.049). No evidence was revealed that ALS caused changes in BP. Conclusions: This study provides genetic support for a causal effect of BP and ALS that increased DBP has a protective effect on ALS, and increased SBP is a risk factor for ALS, which may be related to sympathetic excitability. Blood pressure management is essential in ALS, and CCB may be a promising candidate.

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  • The contrasting findings on hypertension and ALS risk might be because systolic blood pressure is a risk factor and diastolic blood pressure is a protective factor for ALS.

    “The contrasting findings might be because the increment in systolic and diastolic blood pressure might eventually have opposite effects on the risk for ALS; namely, systolic blood pressure might be a risk factor, whereas diastolic blood pressure might be a protective factor, for ALS [46].”

    From Lifestyle and medical conditions in relation to ALS risk and progression—an introduction to the Swedish ALSrisc Study (2024) · cites this paper as [46]

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Cited by

Sorted by citations

Authors
Xia, K., Zhang, L., Tang, L., Huang, T., & Fan, D.
Affiliations
  • Peking University Third Hospital (CN)
  • Peking University (CN)
Corresponding author
  • Huang, Tao
  • Fan, Dongsheng
ORCID
Venue
Orphanet Journal of Rare Diseases
Publisher
Springer Science and Business Media LLC
Published
2022-02-16
Volume
17
Issue
1
Pages
56-56
ISSN
1750-1172 (ISSN-L)
DOI
10.1186/s13023-022-02212-0
PMC
PMC8848798
OpenAlex
W4220882153
Cited by
14
References
2
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 2
FWCI
1.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Orphanet Journal of Rare Diseases (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords
amyotrophic lateral sclerosis, blood pressure, systolic blood pressure, diastolic blood pressure, antihypertensive drugs, calcium channel blockers, causal inference, protective effect, risk factors, blood pressure control
MeSH terms
Amyotrophic Lateral Sclerosis, Blood Pressure, Humans, Risk Factors, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Mendelian Randomization Analysis

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