Three SNPs on chromosomes 12 and 22 were found to be GW significant (p<5×10−8) in the analysis of the hyperthymic temperament as shown in Figure 1. These SNPs are located within or near the MDM1 and FBLN1 (isoform D) genes, respectively, and several other nearby SNPs provide additional support for the association as detailed in Figures 2a and b. These SNPs were not significant in our case-control analysis of BD in the Wave 5 subjects or in the analyses of the other four temperaments (see Table 3). MDM1 encodes a nuclear protein similar to the mouse double minute 1 protein. The fibulin 1 gene (FBLN1) encodes a secreted glycoprotein that may be important for certain developmental processes and contribute to the organization of the extracellular matrix (34). FBLN1 may also play a significant role in modulating the neurotrophic activities of amyloid precursor protein (APP, 35). Four splice variants, A–D, differing in the 3′ end have been identified for FBLN1 (36). Although each variant encodes a different isoform, no functional distinctions have been identified among the four variants. Several other genes of possible interest were identified, although the SNPs did not meet GW significance.
