BackgroundMultiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA.MethodsWe investigated the gene-smoking interactions in DNA methylation using 393 individuals from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). The interaction between rs6933349 and smoking in the risk of developing ACPA-positive RA was further evaluated in a larger portion of the EIRA (1119 controls and 944 ACPA-positive patients with RA), and in the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) (1556 controls and 792 ACPA-positive patients with RA). Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA.ResultsWe identified and replicated one significant gene-environment interaction between rs6933349 and smoking in DNA methylation of cg21325723. This gene-smoking interaction is a novel interaction in the risk of developing ACPA-positive in both Caucasian (multiplicative P value = 0.056; additive P value = 0.016) and Asian populations (multiplicative P value = 0.035; additive P value = 0.00027), and it is mediated through DNA methylation of cg21325723.ConclusionsWe showed that DNA methylation of cg21325723 can mediate the gene-environment interaction between rs6933349 and smoking, impacting the risk of developing ACPA-positive RA, thus being a potential regulator that integrates both internal genetic and external environmental risk factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1276-2) contains supplementary material, which is available to authorized users.

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This paper presents a multidiscipline coupled-field analysis method to study the temperature distribution of an automotive magnetorheological brake with double coils placed on side housing. First, a new apparent viscosity definition was employed to connect the communication of magnetic field, fluid dynamics, and temperature field. Then, the dynamic model of the brake was established to evaluated the rotation law of the brake disk and the total brake time. At last, multi-physics modeling was established with sequencetial coupling methods, which were based on the Maxwell equations, Naiver-Stokes equations and conjugate heat transfer equations. The results indicate that the overall temperature distribution of the MR brake is relatively uniform at a zero magnetic field during the steady state, and the maximum temperature difference is about 9.7°C. During braking process, the temperature variation regularity for radial and axial points is basically the similar, and the maximum temperature appears in the axial working gap, the maximum value is 113°C which is less than the maximum allowable working temperature of the chosen MR fluid. The results can be taken as reference to the design of the MR brake.