BMI and low vitamin D are causal factors for multiple sclerosis A Mendelian Randomization study
BMI and low vitamin D are causal factors for multiple sclerosis A Mendelian Randomization study
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DOI：
10.1212/nxi.0000000000000662
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发表时间：
2020-03-01
影响因子：
8.8
通讯作者：
Dobson, Ruth
中科院分区：
文献类型：
--
作者：
Jacobs, Benjamin M.;Noyce, Alastair J.;Dobson, Ruth
目的更新成人体重指数（BMI）、儿童BMI和维生素D水平对多发性硬化症（MS）风险影响的因果估计。方法采用双样本孟德尔随机化方法进行因果估计。与感兴趣的性状相关的SNP的汇总统计数据来自相关的联盟。主要分析包括随机效应反方差加权荟萃分析，其次是次要敏感性分析。结果由遗传决定的儿童BMI （ORMS 1.24, 95% CI 1.05-1.45, p = 0.011）和成人BMI （ORMS 1.14, 95% CI 1.01-1.30, p = 0.042）增加与MS风险增加相关。在排除了16种与儿童期BMI相关的变异后，由遗传决定的成人BMI对MS风险的影响减弱（ORMS 1.11, 95% CI 0.97-1.28, p = 0.121）。在多变量分析中校正血清维生素D的影响并没有改变这些估计的方向或意义。自然对数转化维生素D水平每增加一个基因决定的单位，多发性硬化症的几率就降低43% （OR 0.57, 95% CI 0.41-0.81, p = 0.001）。结论我们提供了新的证据，证明10岁前的BMI是MS的独立因果危险因素，并加强了维生素D在MS发病机制中的因果作用的证据。
Objective To update the causal estimates for the effects of adult body mass index (BMI), childhood BMI, and vitamin D status on multiple sclerosis (MS) risk. Methods We used 2-sample Mendelian randomization to determine causal estimates. Summary statistics for SNP associations with traits of interest were obtained from the relevant consortia. Primary analyses consisted of random-effects inverse-variance-weighted meta-analysis, followed by secondary sensitivity analyses. Results Genetically determined increased childhood BMI (ORMS 1.24, 95% CI 1.05-1.45, p = 0.011) and adult BMI (ORMS 1.14, 95% CI 1.01-1.30, p = 0.042) were associated with increased MS risk. The effect of genetically determined adult BMI on MS risk lessened after exclusion of 16 variants associated with childhood BMI (ORMS 1.11, 95% CI 0.97-1.28, p = 0.121). Correcting for effects of serum vitamin D in a multivariate analysis did not alter the direction or significance of these estimates. Each genetically determined unit increase in the natural-log-transformed vitamin D level was associated with a 43% decrease in the odds of MS (OR 0.57, 95% CI 0.41-0.81, p = 0.001). Conclusions We provide novel evidence that BMI before the age of 10 is an independent causal risk factor for MS and strengthen evidence for the causal role of vitamin D in the pathogenesis of MS.