One interpretation of the linkage studies is that rare but relatively penetrant variants might contribute to the genetic risk. Nevertheless, it is also possible that the linkage findings could be explained as false positives or the overinterpretation of nonsignificant results. In this respect, it is useful to consider the results of a study of weight in 20,240 siblings (from 9,570 nuclear families) showing that a highly polygenic genetic architecture (such as that underlying MD) can falsely indicate the presence of large-effect loci in a linkage analysis (Hemani et al., 2013).
