NOD2 also illustrates an important property of the underlying genetic model proposed by Dickson et al. [6] that leads to synthetic association, namely that such loci should be amenable to linkage mapping. NOD2 has been consistently mapped by linkage [13]–[17], in contrast to nearly all other reported linkage results for common, complex human disease. The cluster of low frequency variants at the NOD2 locus that confer high risk for disease, which embodies the synthetic association model more generally, is highly tractable by linkage analysis. Therefore, the relative power of linkage and association can be used to make inferences about the rate at which synthetic associations occur.
