Deciphering the causal relationship between blood pressure and regional white matter integrity: A two‐sample Mendelian randomization study

Ye, Zhenyao; Mo, Chen; Liu, Song; Gao, Si; Feng, Li; Zhao, Bingxin; Canida, Travis; Wu, Yi Long; Hatch, Kathryn S.; Ma, Yizhou; Mitchell, Braxton D.; Hong, L. Elliot; Kochunov, Peter; Chen, Chixiang; Chen, Shuo; Ma, Tianzhou

doi:10.1002/jnr.25205

Cited by 3 publications

(2 citation statements)

References 78 publications

(105 reference statements)

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“…Moreover, diastolic blood pressure (DBP) was found to be the main contributing factor, instead of systolic blood pressure (SBP). Ye et al concentrated on FA measures for 39 regions and identified significantly negative causal effects of BP on 21 and 18 WM tracts for SBP and DBP, respectively ( Ye et al, 2023 ). Siedlinski et al conducted a comprehensive assessment, integrating data on SBP, DBP and pulse pressure (PP) with 3,935 BIDPs ( Siedlinski et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

Causal relationships involving brain imaging-derived phenotypes based on UKB imaging cohort: a review of Mendelian randomization studies

Wang,

Wang

et al. 2024

Front. Neurosci.

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The UK Biobank (UKB) has the largest adult brain imaging dataset, which encompasses over 40,000 participants. A significant number of Mendelian randomization (MR) studies based on UKB neuroimaging data have been published to validate potential causal relationships identified in observational studies. Relevant articles published before December 2023 were identified following the PRISMA protocol. Included studies (n = 34) revealed that there were causal relationships between various lifestyles, diseases, biomarkers, and brain image-derived phenotypes (BIDPs). In terms of lifestyle habits and environmental factors, there were causal relationships between alcohol consumption, tea intake, coffee consumption, smoking, educational attainment, and certain BIDPs. Additionally, some BIDPs could serve as mediators between leisure/physical inactivity and major depressive disorder. Regarding diseases, BIDPs have been found to have causal relationships not only with Alzheimer’s disease, stroke, psychiatric disorders, and migraine, but also with cardiovascular diseases, diabetes, poor oral health, osteoporosis, and ankle sprain. In addition, there were causal relationships between certain biological markers and BIDPs, such as blood pressure, LDL-C, IL-6, telomere length, and more.

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Section: Resultsmentioning

confidence: 99%

Causal relationships involving brain imaging-derived phenotypes based on UKB imaging cohort: a review of Mendelian randomization studies

Wang,

Wang

et al. 2024

Front. Neurosci.

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“…However, there have been more debates and uncertainties surrounding the effect of DBP on brain structures and cognitive function compared with SBP [55,56]. Nevertheless, both genetically proxied and regular measurements of SBP and DBP have shown diverse causal effects or significant associations with various targets and regional effects related to white matter fractional anisotropy tracks, brain structures, white matter lesions, cortical volume, and cerebral blood flow [56][57][58][59]. The relationship between blood pressure and brain aging is complex, multifactorial [60], time-dependent, or even nonlinear [61].…”

Section: Discussionmentioning

confidence: 99%

Elevated blood pressure accelerates white matter brain aging among late middle-aged women: a Mendelian Randomization study in the UK Biobank

Feng,

Ye,

et al. 2023

Journal of Hypertension

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Background: Elevated blood pressure (BP) is a modifiable risk factor associated with cognitive impairment and cerebrovascular diseases. However, the causal effect of BP on white matter brain aging remains unclear. Methods: In this study, we focused on N = 228 473 individuals of European ancestry who had genotype data and clinical BP measurements available (103 929 men and 124 544 women, mean age = 56.49, including 16 901 participants with neuroimaging data available) collected from UK Biobank (UKB). We first established a machine learning model to compute the outcome variable brain age gap (BAG) based on white matter microstructure integrity measured by fractional anisotropy derived from diffusion tensor imaging data. We then performed a two-sample Mendelian randomization analysis to estimate the causal effect of BP on white matter BAG in the whole population and subgroups stratified by sex and age brackets using two nonoverlapping data sets. Results: The hypertension group is on average 0.31 years (95% CI = 0.13–0.49; P < 0.0001) older in white matter brain age than the nonhypertension group. Women are on average 0.81 years (95% CI = 0.68–0.95; P < 0.0001) younger in white matter brain age than men. The Mendelian randomization analyses showed an overall significant positive causal effect of DBP on white matter BAG (0.37 years/10 mmHg, 95% CI 0.034–0.71, P = 0.0311). In stratified analysis, the causal effect was found most prominent among women aged 50–59 and aged 60–69. Conclusion: High BP can accelerate white matter brain aging among late middle-aged women, providing insights on planning effective control of BP for women in this age group.

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Association between allostatic load and accelerated white matter brain aging: findings from the UK Biobank

Feng,

Ye,

et al. 2024

Preprint

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White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its causal association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting and doubly robust methods, were used to evaluate the impact of AL on WM BAG adjusting for age, sex, socioeconomic, and lifestyle behaviors. We found increasing one AL score unit significantly increased WM BAG by 0.29 years in association analysis and by 0.33 years in Mendelian randomization causal analysis. The age- and sex-stratified analysis showed consistent results among participants 45-54 and 55-64 years old, with no significant sex difference. This study demonstrated that higher chronic stress caused accelerated brain aging, highlighting the importance of stress management in reducing dementia and neurodegenerative disease risks.

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Deciphering the causal relationship between blood pressure and regional white matter integrity: A two‐sample Mendelian randomization study

Cited by 3 publications

References 78 publications

Causal relationships involving brain imaging-derived phenotypes based on UKB imaging cohort: a review of Mendelian randomization studies

Causal relationships involving brain imaging-derived phenotypes based on UKB imaging cohort: a review of Mendelian randomization studies

Elevated blood pressure accelerates white matter brain aging among late middle-aged women: a Mendelian Randomization study in the UK Biobank

Association between allostatic load and accelerated white matter brain aging: findings from the UK Biobank

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