The coming of age of the Delta Dental Plan of Massachusetts, 1966-1996

The finding by Straub et al. (1995) on 6p22-24 is one of the strongest reports so far in psychiatric genetics. It appears to be substantially replicated by Schwab and collaborators (1995; 1997), and to a lesser extent by Moises et al. (1995). Still, this data does not fulfill the criteria of Lander and Kruglyak (1995) for a confirmed finding in complex disease. There are a number of data sets that do not appear to show linkage. Further genotyping work needs to be done in this area and additional markers in the area would be helpful in the available data sets. It should be noted that the Straub and Kendler dataset (Straub et al., 1995, 1997; Kendler et al., 1996), with 754 affecteds, is substantially larger than any other, and should be weighted concomitant with this. Still, additional data will be necessary before the finding may be firmly accepted. Candidate gene studies have started in this area. The SCA locus is promising on theoretical grounds, but has been only weakly positive in two studies so far. The HLA locus is interesting in relation to autoimmune theories of schizophrenia. There is a long history of HLA studies in schizophrenia with mixed results. HLA is located centromeric to the major positive region identified by Straub, but perhaps not too far to be considered a candidate region. Family-based association studies will be necessary to clarify whether there is a true association in this area. The location identified by Cao et al. (1997) on 6q is promising. Straub and Kendler's data set has been partially tested in this region with negative results. Gejman and co-workers (1997) have recently reported additional positive data in this region from Levinson and Mowry. Additional studies in this area are indicated.