Table 1.

Main characteristics of the studies included in this meta-analysis.

Study	Williams et al.16	Todi et al.11	Patel et al.13	Vazquez et al.15
Country	UK	UK	US	Argentina
Study design	Case-control study	Case-control study	Case-control study	Case-control study
Year	1988	1997	2001	2001
Total number of participants	157 (76 cases and 81 controls)	444 (330 cases and 114 controls)	328 (82 cases and 246 controls)	261 (87 cases and 174 controls)
Participants	Cases: Cases were adult patients with celiac disease who were prospectively recruited from the outpatient clinic of the East Birmingham Hospital, UK. Controls: Controls were individuals without celiac disease who were prospectively recruited from the same outpatient clinic of the same hospital.	Cases: Cases were adult patients with celiac disease who were prospectively recruited from the outpatient clinic of the Castle Hill Hospital, UK. Controls: Controls were individuals without celiac disease who were prospectively recruited from the accident and emergency department of the same hospital. Controls were sex and age-matched to cases.	Cases: Cases were adult patients with celiac disease identified form the database of the Mayo Clinic, Rochester, MN, from January 1993 to June 1998. Controls: Controls were individuals without celiac disease identified from the database of the same hospital at the same period. Controls were sex, age calendar year and geography-matched to cases.	Cases: Cases were consecutive adult patients with celiac disease prospectively recruited from Gastroenterology Hospital of Buenos Aires, Argentina, from July 1997 to December 1997. Controls: Controls were individuals without celiac disease who were prospectively recruited from outpatient clinic of the same hospital at the same period. Controls were sex and age-matched to cases.
Determination of smoking status	Smoking status were obtained from direct interview	Smoking status were obtained from direct interview	Smoking status was obtained from health questionnaires	Smoking status was obtained from health questionnaires
Diagnosis of celiac disease	Celiac disease was diagnosed based on small bowel biopsies showing villous atrophy.	N/A	Celiac disease was diagnosed based on small bowel biopsies showing villous atrophy along with clinical or histological response to gluten-free diet or positive serologies	Celiac disease was diagnosed based on small bowel biopsies showing severe mucosal atrophy, serological test and clinical or histological response to a gluten-free diet
Confounder adjusted in multivariate analysis	None	None	Age and date of visit	None
Quality assessment (Newcastle-Ottawa scale)	Selection: 3 Comparability: 1 Exposure: 2	Selection: 3 Comparability: 2 Exposure: 2	Selection: 3 Comparability: 2 Exposure: 2	Selection: 3 Comparability: 2 Exposure: 2
Study	Suman et al.14	Austin et al.10	Ludvigsson et al.12
Country	UK	UK	Sweden
Study design	Case-control study	Case-control study	Retrospective cohort study
Year	2003	2009	2014
Total number of participants	414 (138 cases and 276 controls)	598 (370 cases and 228 controls)	305,722
Participants	Cases: Cases were patients aged between 18 and 70 years who were diagnosed with celiac disease at the Poole Hospital NHS Trust, UK from 1990 to 2000. Controls: Controls were individuals without celiac disease recruited from ear-nose-throat or orthopedic outpatient clinics of the same center from 2000 to 2001. Controls were sex and age-matched to cases.	Cases: Cases were patients aged 16 years and over with celiac disease identified from the registries of the University Hospital, Nottingham, and Derbyshire Royal Infirmary, Derby, UK. Controls: Controls were individuals without celiac disease randomly identified from the general practitioner registry of the Nottingham Family Health Services. Controls were sex and age-matched to cases.	Participants were construction workers who underwent annual health examination provided by the Swedish national occupational health service from 1971 to 1993. Participants were categorized into current, former and never smokers at the entrance of cohort. Individuals with history of celiac disease prior to the first examination were excluded.
Determination of smoking status	Smoking status were obtained from direct interview	Smoking status was obtained from postal health questionnaires. National smoking data were also used as a second comparator to allow for possible bias and sampling error as a consequence of a low response rate.	Smoking status was obtained from health questionnaires and a face-to-face interview by dedicated nurses.
Diagnosis of celiac disease	Celiac disease was diagnosed from clinical presentation, histology of small bowel biopsies consistent with celiac disease and clinical or histological response to gluten-free diet	Celiac disease was diagnosed based on small bowel histology showing villous atrophy and clinical or histological response to gluten withdrawal	Celiac disease was diagnosed based on duodenal and jejunal biopsies showing villous atrophy. Data of the biopsies were obtained from 28 pathology department across the Sweden from October 2006 to February 2008
Confounder adjusted in multivariate analysis	None	None	Age, sex and decade
Quality assessment (Newcastle-Ottawa scale)	Selection: 3 Comparability: 2 Exposure: 2	Selection: 3 Comparability: 2 Exposure: 2	Selection: 3 Comparability: 1 Outcome: 3

ICD: International classification of disease; MONICA: multinational monitoring of trends and determinants in cardiovascular disease; IgA EMA: immunoglobulin A class antiendomysial antibody; IgA AGA: immunoglobulin A class antigliadin antibody; anti-EMA: antiendomysial antibody; anti-tTG: antitransglutaminase antibody.