Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Center for Health Care Research and Policy, Case Western Reserve School of Medicine, Cleveland, OH, USA.
Mult Scler Relat Disord. 2023 Nov;79:104964. doi: 10.1016/j.msard.2023.104964. Epub 2023 Aug 28.
Epidemiologic studies have established obesity as a risk factor for multiple sclerosis (MS). These studies relied on body-mass index (BMI) and body size silhouettes as the primary measures of obesity. Unfortunately, the causal mechanisms through which obesity confers MS risk are not yet known.
To investigate the causal effects of multiple specific measures of body fat on MS risk in populations of European descent, using Mendelian randomization (MR).
MR is a genetic instrumental variable analysis utilizing genome-wide association (GWA) summary statistics to infer causality between phenotypes. MR analyses were performed to investigate the relationships between seven measures of body fat (BMI, waist-hip ratio, visceral adipose tissue [VAT], subcutaneous adipose tissue, and arm-, leg-, and trunk-fat to total body fat ratio) and MS risk.
Only BMI and VAT were significantly associated with MS risk in separate MR analyses (β=0.27, p<0.001; β=0.28, p=0.006). High correlation between BMI and VAT instruments suggest that two-sample MR associations for BMI and VAT likely capture the same causal mechanisms.
BMI and VAT were causally associated with MS risk in European populations, though their effects do not appear independent, suggesting overlap in the role of overall body mass and visceral obesity in MS pathogenesis.
流行病学研究已经确定肥胖是多发性硬化症（MS）的一个风险因素。这些研究依赖于体重指数（BMI）和体型轮廓作为肥胖的主要衡量标准。不幸的是，肥胖导致 MS 风险的因果机制尚不清楚。
利用孟德尔随机化（MR）研究在欧洲血统人群中，多种特定身体脂肪指标对 MS 风险的因果影响。
MR 是一种基于全基因组关联（GWA）汇总统计数据的遗传工具变量分析，用于推断表型之间的因果关系。进行了 MR 分析，以研究七种身体脂肪指标（BMI、腰臀比、内脏脂肪组织 [VAT]、皮下脂肪、手臂、腿部和躯干脂肪与总身体脂肪的比例）与 MS 风险之间的关系。
只有 BMI 和 VAT 在单独的 MR 分析中与 MS 风险显著相关（β=0.27，p<0.001；β=0.28，p=0.006）。BMI 和 VAT 工具之间的高度相关性表明，BMI 和 VAT 的两样本 MR 关联可能捕获了相同的因果机制。
BMI 和 VAT 与欧洲人群的 MS 风险存在因果关系，但它们的影响似乎并不独立，这表明总体体重和内脏肥胖在 MS 发病机制中的作用存在重叠。
