Tests of random mating for a highly polymorphic locus: application to HLA data

Testing for random mating at an HLA locus is a difficult problem because of the highly polymorphic nature of the HLA loci. We discuss some methodological issues and propose several tests. A simulation study is conducted to evaluate these tests. The single allele test and the shared allele test deal with small sample sizes by aggregating the data in different ways. The shared allele test is found to be a more powerful method of detecting non-random mating patterns involving a deficiency or an excess of similar genotypes than the single allele test. We show that random mating of couple at the genotype level implies the random mating of couple at the allele level. Several multi-allele approaches are proposed for large population-based data sets. Among them, the corrected allele-table test performs better than the generalized Wald test in terms of power and size. These methods are then applied to an HLA data set of Caucasian couples, and no solid evidence for non-random mating at the HLA A, B, and DR loci is found.