TY - JOUR
T1 - The causal effect of HbA1c on white matter brain aging by two-sample Mendelian randomization analysis
AU - Tian, Cheng
AU - Ye, Zhenyao
AU - McCoy, Rozalina G.
AU - Pan, Yezhi
AU - Bi, Chuan
AU - Gao, Si
AU - Ma, Yizhou
AU - Chen, Mo
AU - Yu, Jiaao
AU - Lu, Tong
AU - Hong, L. Elliot
AU - Kochunov, Peter
AU - Ma, Tianzhou
AU - Chen, Shuo
AU - Liu, Song
N1 - Publisher Copyright:
Copyright © 2024 Tian, Ye, McCoy, Pan, Bi, Gao, Ma, Chen, Yu, Lu, Hong, Kochunov, Ma, Chen and Liu.
PY - 2023
Y1 - 2023
N2 - Background: Poor glycemic control with elevated levels of hemoglobin A1c (HbA1c) is associated with increased risk of cognitive impairment, with potentially varying effects between sexes. However, the causal impact of poor glycemic control on white matter brain aging in men and women is uncertain. Methods: We used two nonoverlapping data sets from UK Biobank cohort: gene-outcome group (with neuroimaging data, (N = 15,193; males/females: 7,101/8,092)) and gene-exposure group (without neuroimaging data, (N = 279,011; males/females: 122,638/156,373)). HbA1c was considered the exposure and adjusted “brain age gap” (BAG) was calculated on fractional anisotropy (FA) obtained from brain imaging as the outcome, thereby representing the difference between predicted and chronological age. The causal effects of HbA1c on adjusted BAG were studied using the generalized inverse variance weighted (gen-IVW) and other sensitivity analysis methods, including Mendelian randomization (MR)-weighted median, MR-pleiotropy residual sum and outlier, MR-using mixture models, and leave-one-out analysis. Results: We found that for every 6.75 mmol/mol increase in HbA1c, there was an increase of 0.49 (95% CI = 0.24, 0.74; p-value = 1.30 × 10−4) years in adjusted BAG. Subgroup analyses by sex and age revealed significant causal effects of HbA1c on adjusted BAG, specifically among men aged 60–73 (p-value = 2.37 × 10−8). Conclusion: Poor glycemic control has a significant causal effect on brain aging, and is most pronounced among older men aged 60–73 years, which provides insights between glycemic control and the susceptibility to age-related neurodegenerative diseases.
AB - Background: Poor glycemic control with elevated levels of hemoglobin A1c (HbA1c) is associated with increased risk of cognitive impairment, with potentially varying effects between sexes. However, the causal impact of poor glycemic control on white matter brain aging in men and women is uncertain. Methods: We used two nonoverlapping data sets from UK Biobank cohort: gene-outcome group (with neuroimaging data, (N = 15,193; males/females: 7,101/8,092)) and gene-exposure group (without neuroimaging data, (N = 279,011; males/females: 122,638/156,373)). HbA1c was considered the exposure and adjusted “brain age gap” (BAG) was calculated on fractional anisotropy (FA) obtained from brain imaging as the outcome, thereby representing the difference between predicted and chronological age. The causal effects of HbA1c on adjusted BAG were studied using the generalized inverse variance weighted (gen-IVW) and other sensitivity analysis methods, including Mendelian randomization (MR)-weighted median, MR-pleiotropy residual sum and outlier, MR-using mixture models, and leave-one-out analysis. Results: We found that for every 6.75 mmol/mol increase in HbA1c, there was an increase of 0.49 (95% CI = 0.24, 0.74; p-value = 1.30 × 10−4) years in adjusted BAG. Subgroup analyses by sex and age revealed significant causal effects of HbA1c on adjusted BAG, specifically among men aged 60–73 (p-value = 2.37 × 10−8). Conclusion: Poor glycemic control has a significant causal effect on brain aging, and is most pronounced among older men aged 60–73 years, which provides insights between glycemic control and the susceptibility to age-related neurodegenerative diseases.
KW - HbA1c
KW - Mendelian randomization
KW - brain aging
KW - gene
KW - neuroimaging
KW - white matter integrity
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U2 - 10.3389/fnins.2023.1335500
DO - 10.3389/fnins.2023.1335500
M3 - Article
AN - SCOPUS:85182982890
SN - 1662-4548
VL - 17
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 1335500
ER -