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Epidemiology and Population Health

Causality of abdominal obesity on cognition: a trans-ethnic Mendelian randomization study

Abstract

Background

Obesity has been associated with cognition in observational studies; however, whether its effect is confounding or a reverse causality remains inconclusive. This study aimed to investigate the causal relationships of overall obesity, measured by body mass index (BMI), and abdominal adiposity, measured by waist–hip ratio adjusted for BMI (WHRadjBMI), and cognition across European and Asian populations using Mendelian randomization (MR) analysis.

Methods

We used publicly available genome-wide association study (GWAS) summary data of European ancestry, including BMI (n = 322,154) and WHRadjBMI (n = 210,088) from the GIANT consortium, and cognition performance (n = 257,828) from the UK Biobank and COGENT consortium. Data for individuals of Asian ancestry were retrieved from Taiwan Biobank to perform GWAS for BMI (n = 65,689), WHRadjBMI (n = 65,683), and Mini-Mental State Examination (MMSE, n = 21,273). MR analysis was carried out using the inverse-variance weighted method for the main results. Further, we examined the overall pleiotropy by MR-Egger intercept, and detected and adjusted for possible outliers using MR PRESSO.

Results

No causal effect of BMI on cognition performance (beta [95% CI] = 0.00 [−0.07, 0.07], p value = 0.91) was found for Europeans; however, a 1-SD increase in WHRadjBMI was associated with a 0.07 standardized score decrease in cognition performance (beta [95% CI] = −0.07 [−0.12, −0.02], p value = 0.006). Further, no causal effect of BMI on MMSE (beta [95% CI] = 0.01 [−0.08, 0.10], p = 0.91) was found for Asians; however, a 1-SD increase in WHRadjBMI was associated with a 0.17 standardized score decrease in MMSE (beta [95% CI] = −0.17 [−0.30, −0.03], p = 0.02). In both populations, overall pleiotropy was not detected, and outliers did not affect the robustness of the main findings.

Conclusions

This trans-ethnic MR study reveals that abdominal adiposity, as measured by WHR adjusted for BMI, impairs cognition, whereas weak evidence suggests that BMI impairs cognition.

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Fig. 1: The Mendelian randomization (MR) association between obesity-related traits and cognitive performance in the European population.
Fig. 2: The Mendelian randomization (MR) association between obesity-related traits and MMSE in the Asian population.
Fig. 3: The Mendelian randomization (MR) association between cognitive performance and obesity-related traits in the European population.

Data availability

This study used publicly available GWAS summary statistics from the GIANT consortium, the UK Biobank, and COGENT consortium. In terms of individual data from the Taiwan Biobank, interested researchers can apply the Taiwan Biobank through formal application biobank@gate.sinica.edu.tw.

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Acknowledgements

This work was supported by National Health Research Institutes, Taiwan (NHRI-EX109-10931PI, NHRI-EX110-10931PI, NHRI-EX111-10931PI) and China Medical University, Taiwan (CMU110-MF-24). This study was posted without peer review on the preprint server medRxiv.

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Conceptualized the study: SHW, CSW. Performed the analysis: SHW, MHS, and PCH. Wrote the paper: SHW, CSW. Critically revised the paper: MHS, CYC, YFL, YAF, PCH, and YJP. All authors reviewed and approved the final version of the paper.

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Correspondence to Chi-Shin Wu.

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CYC is an employee of Biogen. The remaining authors declare no competing interests.

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Wang, SH., Su, MH., Chen, CY. et al. Causality of abdominal obesity on cognition: a trans-ethnic Mendelian randomization study. Int J Obes 46, 1487–1492 (2022). https://doi.org/10.1038/s41366-022-01138-8

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