脂联素
孟德尔随机化
内科学
医学
维生素D与神经学
瘦素
肥胖
优势比
内分泌学
置信区间
体质指数
生物
胰岛素抵抗
基因型
遗传学
基因
遗传变异
作者
Adil Harroud,Despoina Manousaki,Guillaume Butler‐Laporte,Ruth E. Mitchell,George Davey Smith,J. Brent Richards,Sergio E. Baranzini
标识
DOI:10.1177/1352458521995484
摘要
Obesity is associated with increased risk of multiple sclerosis (MS); however, the underlying mechanisms remain unclear.To determine the extent to which decreased vitamin D bioavailability and altered levels of adiponectin and leptin mediate the association between obesity and MS.We performed Mendelian randomization (MR) analyses to estimate the effects on MS of body mass index (BMI), 25-hydroxyvitamin D (25OHD), adiponectin, and leptin levels in a cohort of 14,802 MS cases and 26,703 controls. We then estimated the proportion of the effect of obesity on MS explained by these potential mediators.Genetic predisposition to higher BMI was associated with increased MS risk (odds ratio (OR) = 1.33 per standard deviation (SD), 95% confidence interval (CI) = 1.09-1.63), while higher 25OHD levels reduced odds of MS (OR = 0.72 per SD, 95% CI = 0.60-0.87). In contrast, we observed no effect of adiponectin or leptin. In MR mediation analysis, 5.2% of the association between BMI and MS was attributed to obesity lowering 25OHD levels (95% CI = 0.3%-31.0%).This study found that a minority of the increased risk of MS conferred by obesity is mediated by lowered vitamin D levels, while leptin and adiponectin had no effect. Consequently, vitamin D supplementation would only modestly reverse the effect of obesity on MS.
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