Shi-Heng Wang1,2, Mei-Hsin Su1, Chia-Yen Chen3,4, Yen-Feng Lin5, Yen-Chen A Feng6, Po-Chang Hsiao6, Yi-Jiun Pan7, Chi-Shin Wu8,9. 1. Department of Occupational Safety and Health, College of Public Health, China Medical University, Taichung, Taiwan. 2. Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan. 3. Biogen, Cambridge, MA, USA. 4. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. 5. Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan. 6. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. 7. School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. 8. National Center for Geriatrics and Welfare Research, National Health Research Institutes, Miaoli, Taiwan. chishinwu@nhri.edu.tw. 9. Department of Psychiatry, National Taiwan University Hospital, Yunlin Branch, Yunlin, Taiwan. chishinwu@nhri.edu.tw.
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.
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.
Authors: Jennifer H Fergenbaum; Sharon Bruce; Wendy Lou; Anthony J G Hanley; Carol Greenwood; T Kue Young Journal: Obesity (Silver Spring) Date: 2009-05-28 Impact factor: 5.002
Authors: Mar Ariza; Maite Garolera; Maria Angeles Jurado; Isabel Garcia-Garcia; Imma Hernan; Consuelo Sánchez-Garre; Maria Vernet-Vernet; Maria Jose Sender-Palacios; Idoia Marques-Iturria; Roser Pueyo; Barbara Segura; Ana Narberhaus Journal: PLoS One Date: 2012-07-25 Impact factor: 3.240
Authors: Kushan De Silva; Ryan T Demmer; Daniel Jönsson; Aya Mousa; Helena Teede; Andrew Forbes; Joanne Enticott Journal: PLoS One Date: 2022-06-09 Impact factor: 3.752