Department of Occupational Safety and Health, College of Public Health, China Medical University, Taichung, Taiwan.
Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
Int J Obes (Lond). 2022 Aug;46(8):1487-1492. doi: 10.1038/s41366-022-01138-8. Epub 2022 May 10.
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.
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.
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.
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.
肥胖与观察性研究中的认知有关；然而，其影响是混杂因素还是反向因果关系仍不清楚。本研究旨在使用孟德尔随机化（MR）分析，针对欧洲和亚洲人群，调查整体肥胖（由体重指数（BMI）衡量）和腹部肥胖（由 BMI 校正的腰臀比（WHRadjBMI）衡量）与认知之间的因果关系。
我们使用了 GIANT 联盟提供的欧洲血统人群的公开全基因组关联研究（GWAS）汇总数据，包括 BMI（n=322154）和 WHRadjBMI（n=210088），以及 UK Biobank 和 COGENT 联盟的认知表现（n=257828）。从台湾生物银行获取亚洲血统个体的 GWAS 数据，用于 BMI（n=65689）、WHRadjBMI（n=65683）和 Mini-Mental State Examination（MMSE，n=21273）。主要结果采用逆方差加权法进行 MR 分析。此外，我们通过 MR-Egger 截距检查了整体多效性，并使用 MR PRESSO 检测和调整了可能的异常值。
在欧洲人群中，BMI 对认知表现无因果影响（β[95%CI] = 0.00[-0.07, 0.07]，p 值=0.91）；然而，WHRadjBMI 增加 1-SD 与认知表现的 0.07 个标准化分数下降相关（β[95%CI] = -0.07[-0.12, -0.02]，p 值=0.006）。此外，在亚洲人群中，BMI 对 MMSE 无因果影响（β[95%CI] = 0.01[-0.08, 0.10]，p 值=0.91）；然而，WHRadjBMI 增加 1-SD 与 MMSE 的 0.17 个标准化分数下降相关（β[95%CI] = -0.17[-0.30, -0.03]，p 值=0.02）。在两个人群中，均未检测到整体多效性，异常值并未影响主要发现的稳健性。
这项跨种族的 MR 研究表明，腹部肥胖（由 BMI 校正的腰臀比衡量）会损害认知，而微弱的证据表明 BMI 会损害认知。
