A genetic model is discussed for recessively inherited disorders that do not follow a single-locus Mendelian pattern of inheritance. Further complexity arising from variable age of onset is also discussed. Methods of statistical analysis of family data using the likelihood principle are described for such complex disorders. The methods are exemplified using data on families of prelingual deafness and vitiligo.

Vitiligo is a dermatological disorder in man that shows familial aggregation. We performed segregation analysis on data pertaining to vitiligo on members of 147 pedigrees each ascertained through a single proband, and tested various non-genetic, and one-locus and two-locus genetic models. Non-genetic and one-locus genetic models were rejected in favour of a two-locus model postulating epistatic interaction of recessive alleles in the aetiology of vitiligo. The present results show that vitiligo is not a single-locus disorder and substantiate our earlier inference, drawn on the basis of nuclear-family data, of multilocus involvement in the pathogenesis of vitiligo.