HLA haplotype sharing in rheumatoid arthritis sibships: risk estimates in siblings

The distribution of the number of parental HLA haplotypes shared by sibs with rheumatoid arthritis (RA) has been used to obtain information on the genetics of the disease. Thirty-four RA sibships (25 sib-pairs, 9 sib-trios) were ascertained, all of which were HLA typed and which satisfied the 1958 American Rheumatism Association criteria for "definite" RA. These were combined with other published but nonoverlapping data from the literature; thus, 143 sib-pairs, 36 sib-trios and 4 sibquads were identified. The affected RA sibs shared two, one and zero parental HLA haplotypes in a ratio of 40: 45: 15 which was significantly different from random expectations (p less than 0.05). Risk estimates for sibs of probands for those sharing two, one and zero parental HLA haplotypes were 6.2%, 3.5% and 2.3% respectively. Risks subdivided by DR genotype of the proband are also calculated, the highest (8.7%) being for sibs sharing two haplotypes with a proband carrying at least one DR4 allele. The manuscript also considers genetic information in relatives other than siblings; an extension of the affected relative pair haplotype sharing method to second and third degree kinships is presented.