Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Population Health Sciences, Bristol Medical School, University of Bristol, United Kingdom.
PLoS Biol. 2020 Nov 30;18(11):e3000973. doi: 10.1371/journal.pbio.3000973. eCollection 2020 Nov.
The causes of multiple sclerosis (MS) remain unknown. Smoking has been associated with MS in observational studies and is often thought of as an environmental risk factor. We used two-sample Mendelian randomization (MR) to examine whether this association is causal using genetic variants identified in genome-wide association studies (GWASs) as associated with smoking. We assessed both smoking initiation and lifetime smoking behaviour (which captures smoking duration, heaviness, and cessation). There was very limited evidence for a meaningful effect of smoking on MS susceptibility as measured using summary statistics from the International Multiple Sclerosis Genetics Consortium (IMSGC) meta-analysis, including 14,802 cases and 26,703 controls. There was no clear evidence for an effect of smoking on the risk of developing MS (smoking initiation: odds ratio [OR] 1.03, 95% confidence interval [CI] 0.92-1.61; lifetime smoking: OR 1.10, 95% CI 0.87-1.40). These findings suggest that smoking does not have a detrimental consequence on MS susceptibility. Further work is needed to determine the causal effect of smoking on MS progression.
多发性硬化症（MS）的病因仍不清楚。观察性研究表明，吸烟与 MS 有关，通常被认为是环境风险因素。我们使用两样本 Mendelian 随机化（MR）方法，利用全基因组关联研究（GWAS）中发现的与吸烟相关的遗传变异，来检验这种关联是否具有因果关系。我们评估了吸烟起始和终生吸烟行为（包括吸烟持续时间、吸烟量和戒烟）对 MS 的影响。使用国际多发性硬化症遗传学联合会（IMSGC）荟萃分析的汇总统计数据，包括 14802 例病例和 26703 例对照，对吸烟对 MS 易感性的影响进行了评估，结果表明吸烟对 MS 易感性的影响非常有限。没有明确的证据表明吸烟会增加 MS 的发病风险（吸烟起始：比值比 [OR] 1.03，95%置信区间 [CI] 0.92-1.61；终生吸烟：OR 1.10，95% CI 0.87-1.40）。这些发现表明，吸烟对 MS 易感性没有不利影响。需要进一步研究来确定吸烟对 MS 进展的因果影响。
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