1697-P: Waist Circumference, Hippocampal Volume, and Cognitive Impairment—A Mendelian Randomization

The Relationship Between Central Obesity, Cognitive Function, Structural Brain Outcomes: A Mendelian Randomization Study We investigated the relationship between central obesity and cognitive function, brain structure using a Mendelian randomisation (MR). Our exposures were genetic instruments for waist circumstance (WC, 65 variants) and our outcomes were cognitive performance and hippocampal volumes. We used conventional inverse-variance weighted (IVW) MR as the primary analysis method, alongside MR sensitivity analyses. Using IVW, genetic liability to WC was associated with cognitive performance (exponentiated ß=-0.16, 95%CI=0.07; 0.24), volume of left hippocampus (expß=-0.15, 95%CI=0.02; 0.27) and volume of right hippocampus (c=-0.14, 95%CI=0.01; 0.27). Furthermore, we found two variants in hippocampal volume that were also associated with WC, these two variants were associated with cognitive function (expß = 0.006, 95%CI=0.003; 0.009). Overall, we observed evidence of causal association between genetic instruments for WC and cognitive performance, and volume of hippocampus may be a mediator linking WC with cognitive function. Table 1 MR estimates of the effect of WC on cognitive function and left or right hippocampus volume. Disclosure J.Zhang: None. S.Luan: None. J.Zhou: None.