Familial clustering of rheumatoid arthritis with other autoimmune diseases

Previous studies have shown that rheumatoid arthritis aggregates within fam ilies. However, no formal genetic analysis of rheumatoid arthritis in pedig rees together with other autoimmune diseases has been reported. We hypothes ized that there are genetic factors in common in rheumatoid arthritis and o ther autoimmune diseases. Results of odds-ratio regression and complex segr egation analysis in a sample of 43 Caucasian pedigrees ascertained through a rheumatoid arthritis proband or matched control proband, revealed a very strong genetic influence on the occurrence of both rheumatoid arthritis and other autoimmune diseases. In an analysis of rheumatoid arthritis alone, o nly one inter-class measure, parent-sibling, resulted in positive evidence of aggregation. However, three inter-class measures (parent-sibling, siblin g-offspring, and parent-offspring pairs) showed significant evidence of fam ilial aggregation with odds-ratio regression analysis of rheumatoid arthrit is together with all other autoimmune diseases. Segregation analysis of rhe umatoid arthritis alone revealed that the mixed model, including both polyg enic and major gene components, was the most parsimonious. Similarly, segre gation analysis of rheumatoid arthritis together with other autoimmune dise ases revealed that a mixed model fitted the data significantly better than either major gene or polygenic models. These results were consistent with a previous study which concluded that several genes, including one with a ma jor effect, is responsible for rheumatoid arthritis in families. Our data s howed that this conclusion also held when the phenotype was defined as rheu matoid arthritis and/or other autoimmune diseases, suggesting that several major autoimmune diseases result from pleiotropic effects of a single major gene on a polygenic background.