The intrafamilial transmission of rheumatoid arthritis. 3. The lack of support for a genetic hypothesis.

EVER since the days of WILLIAM HEBERDEN [I], it has been commonly held that there exists an appreciable genetic component in the etiology of rheumatoid arthritis [l-4]. However, a recent review of the subject [5] concludes “With improved technics in the design and execution of family studies the evidence for familial aggregation has become less impressive and is, in fact, open to question”. Another [6] concludes “ . . . the available studies give little support to any genetic cause of RA”. On the other hand, LAWRENCE [7] is impressed by some familial aggregation of severe disease which is not apparent for the milder cases. The present investigation was designed to measure the prevalence of rheumatoid arthritis among several classes of relatives, biological and marital, of rheumatoid probands; the latter were selected in such manner as to encompass a larger segment of the gradient of the disease than is generally studied on the assumption that thereby the “true” state of affairs might be revealed. It is our purpose now to examine the data in hand to see if they conform to any of the simpler genetic hypotheses, and if not, to ascertain the possible magnitude of the genetic contribution in more general terms. The design of the study as well as the method of measuring rheumatoid arthritis, referred to as the RA measure, with its validation, its sensitivity (86 per cent), and its specificity (98 per cent) have been described in the first 2 papers of this series. Forty-nine family clusters are involved with members distributed as follows : Key persons or probands 49 Spouses of key persons 49 Siblings 48 Spouses of siblings 49 cousins 83 Unrelated persons 46 Six of the 49 key persons proved on final analysis not to have rheumatoid arthritis.