Pedigrees, or family trees, are directed graphs used to identify sites of the genome that are correlated with the presence or absence of a disease. With the advent of genotyping and sequencing technologies, there has been an explosion in the amount of data available, both in the number of individuals and in the number of sites. Some pedigrees number in the thousands of individuals. Meanwhile, analysis methods have remained limited to pedigrees of < 100 individuals which limits analyses to many small independent pedigrees.

Disease models, such those used for the linkage analysis log-odds (LOD) estima- tor, have similarly been limited. This is because linkage anlysis was originally designed with a different task in mind, that of ordering the sites in the genome, before there were technologies that could reveal the order. LODs are difficult to interpret and nontrivial to extend to consider interactions among sites. These de- velopments and difficulties call for the creation of modern methods of pedigree analysis.

Drawing from recent advances in graphical model inference and transducer theory, we introduce a simple yet powerful formalism for expressing genetic disease mod- els. We show that these disease models can be turned into accurate and efficient estimators. The technique we use for constructing the variational approximation has potential applications to inference in other large-scale graphical models. This method allows inference on larger pedigrees than previously analyzed in the liter- ature, which improves disease site prediction.