HLA-LINKED RHEUMATOID-ARTHRITIS

Twenty-eight pedigrees were ascertained through pairs of first-degree relatives diagnosed with rheumatoid arthritis (RA). RA was confirmed i n 77 pedigree members including probands; the absence of disease was v erified in an additional 261 pedigree members. Pedigree members were s erologically typed for HLA. We used likelihood analysis to statistical ly characterize the HLA-linked RA susceptibility locus. The genetic mo del assumed tight linkage to HLA. The analysis supported the existence of an HLA-linked RA susceptibility locus, estimated the susceptibilit y allele frequency as 2.16%, and estimated the lifetime penetrance as 41% in male homozygotes and as 48% in female homozygotes. Inheritance was recessive in males and was nearly recessive in females. In additio n, the analysis attributed 78% of the variance within genotypes to gen etic or environmental effects shared by siblings. The genetic model in ferred in this analysis is consistent with previous association, linka ge, and familial aggregation studies of RA. The inferred HLA-linked RA susceptibility locus accounts for approximately one-half of familial RA, although it accounts for only approximately one-fifth of the RA in the population. Although other genes may account for the remaining fa milial RA, a large portion of RA cases may occur sporadically.