Department of Neurology, University of California San Francisco, San Francisco, CA, USA/Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA/Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK/Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Mult Scler. 2021 Dec;27(14):2150-2158. doi: 10.1177/13524585211001781. Epub 2021 Mar 22.
Higher childhood body mass index (BMI) has been associated with an increased risk of multiple sclerosis (MS).
To evaluate whether childhood BMI has a causal influence on MS, and whether this putative effect is independent from early adult obesity and pubertal timing.
We performed Mendelian randomization (MR) using summary genetic data on 14,802 MS cases and 26,703 controls. Large-scale genome-wide association studies provided estimates for BMI in childhood ( = 47,541) and adulthood ( = 322,154). In multivariable MR, we examined the direct effects of each timepoint and further adjusted for age at puberty. Findings were replicated using the UK Biobank ( = 453,169).
Higher genetically predicted childhood BMI was associated with increased odds of MS (odds ratio (OR) = 1.26/SD BMI increase, 95% confidence interval (CI): 1.07-1.50). However, there was little evidence of a direct effect after adjusting for adult BMI (OR = 1.03, 95% CI: 0.70-1.53). Conversely, the effect of adult BMI persisted independent of childhood BMI (OR = 1.43; 95% CI: 1.01-2.03). The addition of age at puberty did not alter the findings. UK Biobank analyses showed consistent results. Sensitivity analyses provided no evidence of pleiotropy.
Genetic evidence supports an association between childhood obesity and MS susceptibility, mediated by persistence of obesity into early adulthood but independent of pubertal timing.
较高的儿童期体重指数（BMI）与多发性硬化症（MS）的风险增加有关。
评估儿童期 BMI 是否对 MS 有因果影响，以及这种假定的影响是否独立于成年早期肥胖和青春期时间。
我们使用 14802 例 MS 病例和 26703 例对照的汇总遗传数据进行孟德尔随机化（MR）。全基因组关联研究提供了儿童期（=47541）和成年期（=322154）BMI 的估计值。在多变量 MR 中，我们检查了每个时间点的直接影响，并进一步调整了青春期年龄。使用英国生物银行（=453169）进行了复制研究。
较高的遗传预测儿童期 BMI 与 MS 的发病几率增加相关（比值比（OR）=1.26/SD BMI 增加，95%置信区间（CI）：1.07-1.50）。然而，在调整成年 BMI 后，几乎没有直接影响的证据（OR=1.03，95% CI：0.70-1.53）。相反，成年 BMI 的影响独立于儿童期 BMI 持续存在（OR=1.43；95% CI：1.01-2.03）。青春期年龄的增加并没有改变这些发现。英国生物银行的分析结果一致。敏感性分析没有提供多效性的证据。
遗传证据支持儿童肥胖与 MS 易感性之间存在关联，这种关联是通过肥胖持续到成年早期来介导的，但与青春期时间无关。
