The affected sib method. I. Statistical features of the affected sib-pair method

The distribution of the number of HLA haplotypes shared by sibs affected with the same HLA-linked disease can be used to obtain information on the genetics of the disease. Since the inception of the use of sib-pair methods for the analysis of the HLA-associated diseases, the question has been raised of how to include families with more than two affected sibs in the sib-pair analysis. This paper presents appropriate weighting schemes. A procedure for estimating the frequency of the disease allele in the general population, under the assumptions of single-allele recessive, additive, dominant and intermediate models, with negligible recombination (θ = 0) between the disease-predisposing gene and the HLA region, and no selective disadvantage of the trait, is also given. Cluster-sampling techniques are used in the analysis.