Genetic analysis of bipolar disorder: summary of GAW10

Participants in the Bipolar Disorder component of Genetic Analysis Workshop 10 had access to five distributed data sets containing chromosome 18 marker data and five data sets containing chromosome 5 data. A total of 25 groups participated in analyses and applied a myriad of methodologically innovative approaches to these data. Contributors focused on how to: (1) best define the phenotype from the spectrum of affective diagnoses; (2) test for a parent-of-origin effect in the transmission of bipolar illness and assess whether sharing in affected sib pairs depends on the sex of the transmitting parent; (3) evaluate the effects of misspecification of marker allele frequencies; (4) examine the putative candidate loci provided; (5) investigate the mode of inheritance; and (6) perform a meta-analysis to combine multiple data sets in a single analysis. Taken as a whole, the results would appear suggestive, but not definitive for linkage to a bipolar susceptibility locus on chromosome 18. The evidence for linkage appeared to increase as the diagnostic definition of the phenotype was broadened. Multipoint analyses seem to provide less evidence. It is possible that, because adjacent markers may be present in different data sets, the multipoint methods are combining marker data from different studies in a more comprehensive way than single marker analyses. Evidence on chromosome 5 and evidence for candidate loci were minimal. A discussion of problems inherent in combined analyses is given.