肥胖、体脂分布与癫痫亚型之间的因果关系。

Causal relationship among obesity and body fat distribution and epilepsy subtypes.

作者信息

Zhou Kaiping, Yang Huan, Chen Ruomeng, Wang Weiping, Qu Zhenzhen

机构信息

Key Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Front Neurol. 2022 Oct 26;13:984824. doi: 10.3389/fneur.2022.984824. eCollection 2022.

DOI:10.3389/fneur.2022.984824

PMID:36388204

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9644162/

Abstract

OBJECTIVE

The observational studies indicate an association between obesity and epilepsy, but it is unclear whether such an association responds to causality. The objective of this study was to determine the causal relationship between obesity and fat distribution and epilepsy subtypes based on waist circumference, hip circumference (HP), waist-hip ratio (WHR), and body mass index (BMI).

METHODS

A two-sample Mendelian randomization study was conducted separately for the four indicators of obesity and epilepsy and its seven subtypes, with reverse Mendelian randomization and multivariate Mendelian randomization for significant outcomes.

RESULTS

A two-sample Mendelian randomized analysis informed us that waist circumference was a risk factor for juvenile myoclonic epilepsy (beta = 0.0299, = 4.60 × 10). The increase in hip circumference increased the risk of juvenile myoclonic epilepsy and epilepsy, with effect values of 0.0283 ( = 2.01 × 10) and 0.0928 ( = 1.40 × 10), respectively. Furthermore, children with a higher BMI exhibit a higher risk of epilepsy (beta = 0.0148 = 1.05 × 10). The reverse Mendelian randomization study revealed that childhood absence epilepsy increased its BMI (beta = 0.8980, = 7.52 × 10), and juvenile myoclonic epilepsy increased its waist circumference (beta = 0.7322, = 3.26 × 10). Multivariate Mendelian randomization revealed that an increase in hip circumference and waist-hip ratio increased the risk of juvenile myoclonic epilepsy, with an effect value of 0.1051 ( = 9.75 × 10) and 0.1430 ( = 3.99 × 10), respectively, while an increase in BMI and waist circumference instead decreased their risk, with effect values of -0.0951 ( = 3.14 × 10) and-0.0541 ( = 1.71 × 10). In contrast, multivariate Mendelian randomization for childhood absence epilepsy and epilepsy did not identify any independent risk factors.

SIGNIFICANCE

Our findings provide novel evidence in favor of obesity as a risk factor for epilepsy and waist circumference as a risk factor for juvenile myoclonic epilepsy. Increased hip circumference confers an elevated risk of juvenile myoclonic epilepsy and epilepsy (all documented cases), and a high BMI increases the risk of childhood absence epilepsy. With this, new insights are provided into the energy metabolism of epilepsy, which supports further nutritional interventions and the search for new therapeutic targets.

摘要

目的

观察性研究表明肥胖与癫痫之间存在关联，但这种关联是否存在因果关系尚不清楚。本研究的目的是基于腰围、臀围（HP）、腰臀比（WHR）和体重指数（BMI）来确定肥胖及脂肪分布与癫痫亚型之间的因果关系。

方法

针对肥胖的四个指标以及癫痫及其七种亚型分别进行双样本孟德尔随机化研究，并对显著结果进行反向孟德尔随机化和多变量孟德尔随机化分析。

结果

双样本孟德尔随机化分析表明，腰围是青少年肌阵挛性癫痫的一个危险因素（β = 0.0299，P = 4.60×10⁻⁶）。臀围增加会增加青少年肌阵挛性癫痫和癫痫的风险，效应值分别为0.0283（P = 2.01×10⁻⁵）和0.0928（P = 1.40×10⁻⁵）。此外，BMI较高的儿童患癫痫的风险更高（β = 0.0148，P = 1.05×10⁻⁴）。反向孟德尔随机化研究显示，儿童失神癫痫会使其BMI增加（β = 0.8980，P = 7.52×10⁻⁴），青少年肌阵挛性癫痫会使其腰围增加（β = 0.7322，P = 3.26×10⁻⁴）。多变量孟德尔随机化分析显示，臀围和腰臀比增加会增加青少年肌阵挛性癫痫的风险，效应值分别为0.1051（P = 9.75×10⁻⁴）和0.1430（P = 3.99×10⁻⁴），而BMI和腰围增加反而会降低其风险，效应值分别为-0.0951（P = 3.14×10⁻⁴）和-0.0541（P = 1.71×10⁻⁴）。相比之下，针对儿童失神癫痫和癫痫的多变量孟德尔随机化分析未发现任何独立危险因素。