GoTriple - Abdominal obesity and lower gray matter volume: a Mendelian randomization study.

authors

Contributors

Boston University School of Medicine (BUSM) ; Boston University [Boston] (BU),

INSERM, Neuroepidemiology U708, Paris and Bordeaux, France,

Department of Epidemiology, University of Versailles Saint-Quentin-en-Yvelines, Garches, France,

Department of Neurology, Lariboisière Hospital, Paris 7 University, Paris, France,

Statistical Genetics [Munich] ; Max Planck Institute of Psychiatry ; Max-Planck-Gesellschaft-Max-Planck-Gesellschaft,

Epidemiology and Public Health, INSERM U744, Lille, France,

Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296) ; Service NEUROSPIN (NEUROSPIN) ; Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS),

Department of Neurology, Peking Union Medical College Hospital, Beijing, China,

INSERM U897, Université Bordeaux Segalen, Bordeaux, France,

Centre de recherche en épidémiologie et santé des populations (CESP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

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Publisher

HAL CCSD,

Elsevier

Abstract

International audience We investigated the relationship of anthropometric markers of obesity with quantitative magnetic resonance imaging markers of brain aging, including measures of total brain volume (TBV), gray matter volume (GMV), hippocampal volume, white matter hyperintensity volume (WMHV), and brain infarcts, and examined causality using Mendelian randomization (MR). Analyses were performed in 1779 individuals (60.4% women, 72.8 ± 4.1 years of age) from the 3C-Dijon population-based cohort study (N = 1555 for the MR). Larger waist-to-hip-ratio (WHR) and waist circumference (WC) were associated with lower TBV (p = 0.0001 and p = 0.005), and lower GMV (p = 0.0008 and p = 0.003), independently of age, gender, body mass index (BMI), and vascular risk factors. Higher BMI, WC, and WHR were associated with larger WMHV and WC with brain infarcts, before adjusting for vascular risk factors only. We used MR to investigate the inverse relationship between WHR and GMV. One valid instrumental variable was available in women only (rs6905288), which was associated with GMV (p = 0.015). Age and BMI-adjusted effect estimates from the MR analysis confirmed the inverse association between GMV and WHR and are in favor of a causal association.