Table 1. Key studies on the association between smoking and MS.

Study	Study Design	Main Outcome
Study 1 [38]	A prospective cohort study examined 3,052 cases against 457,619 controls.	Reported a relative risk (RR) of 1.48 and concluded that smoking might increase the susceptibility to multiple sclerosis (MS).
Study 2 [23]	A case-control study with 843 cases and 1,209 controls.	Among those with genetic risk factors, smoking increased the risk by a factor of 2.8 in comparison with a factor of 1.4 among those without the genetic risk factors.
Study 3 [46]	This case-control study compared 516 cases with 1,090 controls.	Past smokers and current smokers had a significant risk of developing MS.
Study 4 [39]	A low-quality case-control study in which 81 patients with MS were compared with 81 paired controls.	This study stated that ever smoking could increase the risk of MS by 7.6-fold.
Study 5 [40]	Two Swedish population-based case-control studies consisted of 7,883 cases and 9,264 controls.	This research saw a clear dose-response association between cumulative dose of smoking and MS risk.
Study 6 [37]	This is a cross-sectional survey and longitudinal follow-up of 1,465 patients with clinically definite MS.	MS in smokers progressed from relapsing-remitting (RRMS) to secondary progressive disease (SPMS) faster than in never-smokers.
Study 7 [43]	Retrospective research consisted of 179 cases with a mean follow-up period of 5.3 years.	These results suggest that smoking may be a risk factor for transforming a relapsing-remitting (RRMS) course into a secondary progressive course (SPMS).
Study 8 [47]	Smoking habits in 122 cases were assessed with a median of six years of disease duration.	Compared with never-smokers, ever-smokers were more likely to have a progressive illness.
Study 9 [41]	Smoking status is assessed in a case-control study consisting of 210 cases with clinically proven or laboratory-confirmed MS.	A dose-response relationship between the risk of MS and both duration (years) of smoking and the number of cigarettes smoked daily was observed.
Study 10 [27]	In Sweden, two population-based case-control datasets were used to perform a three-stage gene analysis for NAT1, NAT2, and GSTP1 variants.	They found out NAT1 as a genetic effect modifier of tobacco smoke exposure in MS susceptibility.