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OBJECTIVE: To define interactions between the HLA-DRB1 shared epitope (SE), PTPN22, and smoking in cyclic citrullinated peptide (CCP) antibody- and rheumatoid factor (RF)-positive and -negative rheumatoid arthritis (RA). METHODS: Data on approximately 5,000 RA patients and approximately 3,700 healthy controls recruited from 6 centers in the UK were analyzed; not all centers had both genotype data and smoking data available for study. The magnitude of association was assessed in autoantibody-positive and -negative subgroups. The effect of smoking on antibody status among cases was assessed following adjustment for year of birth and center, using Mantel-Haenszel analysis. Analyses of the combined effects of PTPN22, HLA-DRB1 SE, and smoking were performed using additive and multiplicative models of interaction within a logistic regression framework. RESULTS: The combined effects of PTPN22, HLA-DRB1 SE, and smoking were defined, with no evidence of departure from a multiplicative model. Within the case population, all 3 factors were independently associated with the generation of CCP antibodies (odds ratio [OR] 11.1, P < 0.0001), whereas only HLA-DRB1 SE and smoking were independently associated with RF production (OR 4.4, P < 0.0001). There was some evidence of increasing likelihood of antibody positivity with heavier smoking. Finally, we demonstrated that smoking was associated with the generation of both CCP and RF antibodies (OR 1.7, P = 0.0001). CONCLUSION: PTPN22 appears to be primarily associated with anticitrulline autoimmunity, whereas HLA-DRB1 SE is independently associated with RF. This study has confirmed associations of specific gene-environment combinations with a substantially increased risk of developing RA. Further work is needed to determine how these data can be used to inform clinical practice. [ABSTRACT FROM AUTHOR]

This study compared results obtained on the Wechsler Adult Intelligence Scale-Revised and the Kaufman Adolescent Test and Adult Intelligence; these tests were individually administered to college students with and without learning disabilities. Participants were 30 students with learning disabilities and 30 students without learning disabilities between the ages of 18 and 30. Students were administered both IQ tests and the Peabody Picture Vocabulary Test-Revised, used as a covariate measure. The results were analyzed through a repeated-measures analysis of variance. No significant differences were found between groups or between tests. A significant difference was found for both groups when Performance IQ and Fluid Scale scores were compared. [ABSTRACT FROM AUTHOR]