Our aim was to investigate the association between obesity as measured by BMI or waist circumference and subsequent development of RA, taking gender into account, in a casecontrol study nested within a large population-based, prospective cohort. == Methods == Two previously described cohorts, the Vsterbotten Intervention Programme (VIP) and the Northern Sweden Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) project, were used for this nested casecontrol study [22, Kelatorphan 23]. RA development, adjusted odds ratio (OR) (95% CI), 1 . 13 (1. 00, 1 . 28) per 5 kg/m2, and 1 . 02 (1. 01, 1 . 04) per cm, respectively. An association was also observed for obesity (BMI 30) OR 1 . 45 (1. 07, 1 Kelatorphan . 95), compared with BMI <25. After stratification for sex the associations Kelatorphan were enhanced in men, and attenuated in women. Among men with BMI above normal a 35 times increased risk for RA disease development at 50 years of age or earlier was observed. Abdominal obesity with waist circumference > 102 cm was associated with a 23 times increased risk of RA, but not abdominal obesity (> 88 cm) in women. == Conclusions == Obesity or abdominal obesity, respectively, was independently associated with a modest increase of the risk for subsequent development of RA. This appeared to be relevant mainly for early RA disease onset among men. == Electronic supplementary material == The online version of this article (doi: 10. 1186/s13075-016-1171-2) contains supplementary material, which is available to authorized users. Keywords: Rheumatoid arthritis, Epidemiology, Risk factors, Lifestyle, Obesity, Casecontrol == Background == At the time point when the first symptoms indicating the onset of rheumatoid arthritis (RA) become apparent for the individual, the immune system has been activated for several years. This has been demonstrated by the presence of anti-citrullinated peptide antibodies (ACPA), rheumatoid factor (RF) and up-regulation of cytokines and chemokines in blood samples [1, 2]. The pathogenesis of RA is largely unknown but heritability of approximately 50% for ACPA-positive and approximately 20% for ACPA-negative RA has been shown, and environmental factors are believed to interplay with genetic factors during the early, pre-symptomatic stages [3]. Smoking and periodontal disease have been linked to development of mainly seropositive RA [4, 5]. Obesity could be another possible environmental risk factor due IL6R to the pro-inflammatory nature of the adipose tissue, but studies evaluating the association between body mass index (BMI) and the risk of RA have shown contradictory results [616]. Several studies have reported a positive association between obesity and the risk of RA development, overall [8, 9, 11, 12, 16], in women [6, 10, 16], and in seronegative RA disease development [9, 15]. Negative associations with obesity have been reported in two studies: in RA [7] and ACPA-positive RA [15], respectively, in men. Another two studies reported no statistically significant associations between BMI or BMI categories and RA [13, 14]. The comparison between studies is hampered by differences in methodology, but a recent meta-analysis suggested a 30% increase in the risk of RA overall in obesity compared with normal weight [17]. Generally, BMI based on weight and height measurements has limitations, as the proportion of body fat and the location of the adipose tissue are of importance for the risks associated with obesity. Visceral adipose tissue depots are associated with metabolic disease, whereas subcutaneous adipose tissue might have a protective effect on cardiovascular risk factors [18, 19]. Men with RA have been shown to have increased deposition of intra-abdominal fat and the proportion of visceral fat is associated with cardiovascular risk factors [20]. Moreover, differences have been observed between men and women in body fat distribution or the associations between adipose tissue and comorbidity [1821]. More Kelatorphan profound knowledge of the tentative role of obesity in the phases of RA before symptom onset could improve the possibility of RA disease prevention in high-risk individuals. Our aim was to investigate the association between obesity as measured by BMI or waist circumference and subsequent development of RA, taking gender into account, in a casecontrol study nested within a large population-based, prospective cohort. == Methods == Two previously described cohorts, the Vsterbotten Intervention Programme (VIP) and the Northern Sweden Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) project, were used for this nested casecontrol study [22, 23]. In brief, the VIP was started in 1985, and since 1991 all inhabitants of Vsterbotten County in northern Sweden have been invited to participate in VIP by having health examination visits at 40, 50 and 60 years of age, mainly for screening of cardiovascular risk factors and prevention of cardiovascular morbidity. The Northern Sweden MONICA project has performed population risk factor surveys six times since 1986 in individuals aged 2574 years. Both cohorts are characterized by a high participation rate (7080%) and data on life style factors are collected in a similar manner in both, making merging of data from the two cohorts possible. Demographic and anthropometric data and data on cardiovascular risk factors are collected Kelatorphan through standardised measurements of weight (kg), height (cm) and blood pressure, and through blood sampling and questionnaires. Waist circumference (cm) is measured in the.