Table 1. The main characteristics of the included studies.

1st author and year of publication	Cases	Controls or observational individual	OR or RR(95% CI) versus never-smoking	Information collecting	Type	Diagnostic criteria	Smoking and the onset of MS
Ragnedda 2015 (Norwegian)	894	1,610	2.00(1.68, 2.38) (ever-smoking)	Questionnaire	Case-control	McDonald	Before onset
Ragnedda 2015 (Italian)	617	1,161	1.55(1.28, 1.88) (ever-smoking)	Questionnaire	Case-control	McDonald	Before onset
Simon 2014	1,190	454	1.4(1.1, 1.9) (ever-smoking)	Face interview	Case-control	N/A	Before onset
Gustavsen 2014	530	918	2.29(1.82, 2.89) (ever-smoking)	Questionnaire	Case-control	McDonald or Poser	current
Mansouri 2014	1,217	787	1.93(1.31, 2.73) (ever-smoking)	Face interview	Case-control	McDonald or Poser	Before onset
O’Gorman 2014	560	480	1.9(1.5, 2.5) (ever-smoking) 3.6(2.3, 5.6) (current-smoking) 1.6(1.2, 2.1) (past-smoking)	Questionnaire	Case-control	Physician	Current
Briggs 2014	1,012	576	1.27(1.03, 1.58) (ever-smoking)	Telephone questionnaire	Case-control	McDonald	Before onset
Asadollahi 2013	662	394	1.78(1.22, 2.59) (ever-smoking)	Face or telephone interview	Case-control	McDonald or Poser	Before onset
Hedström 2013	6,990	8,279	1.49(1.40, 1.59) (ever-smoking) 1.56(1.45, 1.67) (current-smoking) 1.35(1.24, 1.47) (past-smoking)	Questionnaire	Case-control	McDonald	Before onset
Ramagopalan 2013	3,157	756	1.32(1.10, 1.60) (ever-smoking)	Questionnaire	Case-control	N/A	Current
Kotzamani 2012	504	591	1.9(1.50, 2.41) (ever-smoking)	Questionnaire	Case-control	N/A	Before onset
Al-Afasy 2010	101	202	1.7(0.9, 2.4) (ever-smoking)	Face interview	Case-control	Neurologist	Before onset
Maghzi 2011	516	1,090	2.67(1.70, 4.21) (ever-smoking)	Questionnaire	Case-control	McDonald	Before onset
Alonso 2011	394	394	1.72(0.90, 3.30) (ever-smoking)	Telephone interview	Case-control	McDonald	Before onset
Simon 2010a	210	420	1.4(1.0, 2.0) (ever-smoking)	Questionnaire	Case-control	N/A	Before onset
Simon 2010b	136	272	1.5(1.0, 2.4) (ever-smoking)	Interview	Case-control	Poser	Before onset
Simon 2010c	96	173	1.4(0.8, 2.4) (ever-smoking)	Questionnaire	Case-control	N/A	Before onset
Carlens 2010	214	277,777	2.5(1.7, 3.6) (ever-smoking) 2.8(1.9, 4.2) (current-smoking) 1.6(0.9, 2.8) (past-smoking)	N/A	Cohort	N/A	Before onset
Jafari 2009	136	204	1.09(0.68, 1.73) (ever-smoking) 1.03(0.61, 1.73) (current-smoking) 1.19(0.65, 2.20) (past-smoking)	Questionnaire	Case-control	McDonald	Before onset
Silva 2009	81	81	2.0(0.9, 4.3) (current-smoking)	Face interview	Case-control	Poser	Current
Russo 2008	94	53	1.83(0.86, 3.87) (ever-smoking)	N/A	Case-control	McDonald	N/A
Pekmezovic 2006	196	210	1.6(1.08, 2.37) (ever-smoking)	Face interview	Case-control	Poser	Before onset
Hernan 2005	210	1,913	1.3(1.0, 1.7) (ever-smoking) 1.4(1.0, 1.9) (current-smoking) 1.0(0.6, 1.8) (past-smoking)	Questionnaire	Case-control	Poser	Before onset
Riise 2003	87	22,312	1.81(1.13, 2.92) (ever-smoking)	Questionnaire	Cohort	Self-report	Before onset
Zorzon 2003	140	131	1.50(0.90, 2.40) (ever-smoking)	Interview	Case-control	McDonald	Before onset
Hernan 2001	314	238,371	1.6(1.2, 2.1) (current-smoking) 1.2(0.9,1.6) (past-smoking)	Questionnaire	Cohort	Physician	Before onset
Ghadirian 2001	200	202	1.6(1.0, 2.4) (ever-smoking)	Face interview	Case-control	N/A	Before onset
Thorogood 1998	114	46,000	1.2(0.8, 1.8) (1–14/day)	N/A	Cohort	Physician	Before onset
Villard 1993	63	17,032	1.5(0.6, 3.3) (ever-smoking)	N/A	Cohort	N/A	Before onset