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Causality of Abdominal Obesity on Cognition: a Trans-ethnic Mendelian Randomization study

By Shi-Heng Wang, Mei-Hsin Su, Chia-Yen Chen, Yen-Feng Lin, Yen-Chen A Feng, Po-Chang Hsiao, Yi-Jiun Pan, Chi-Shin Wu

Posted 18 Oct 2021
medRxiv DOI: 10.1101/2021.10.13.21264895

Obesity has been associated with cognition in observational studies; however, whether its effect is confounding, reverse causality, or causal remains inconclusive. Using two-sample Mendelian randomization (MR) analyses, we investigated the causality of overall obesity, measured by BMI, and abdominal adiposity, measured by waist-hip ratio adjusted for BMI (WHRadjBMI), on cognition. Using summary data from the GIANT consortium, COGENT consortium, and UK Biobank of European ancestry, there was no causal effect of BMI on cognition performance (beta[95% CI]=-0.04[-0.12,0.04], p-value=0.35); however, a 1-SD increase in WHRadjBMI was associated with 0.07 standardized decrease in cognition performance (beta[95% CI]=-0.07[-0.12,-0.02], p=0.006). Using raw data from the Taiwan Biobank of Asian ancestry, there was no causal effect of BMI on cognitive aging (beta[95% CI]=0.00[-0.09,0.09], p-value=0.95); however, a 1-SD increase in WHRadjBMI was associated with a 0.17 standardized decrease in cognitive aging (beta[95% CI]=-0.17[-0.30,-0.03], p=0.02). This trans-ethnic MR study reveals that abdominal adiposity impairs cognition.

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