Searching susceptibility loci for bipolar disorder: a sib pair study on chromosome 12

Background/Aims: Several linkage studies demonstrated that different chromosomal regions are involved in the susceptibility to bipolar disorder. In particular, some genome scans evidenced the role of chromosome 12. For this reason, our group chose this chromosome for a preliminary genome scan on a sample of 137 Italian sib pairs, including at least 1 bipolar subject. Methods: The analyses were carried out by means of DNA extracted from whole blood. DNA samples were genotyped by 19 simple tandem repeat markers (microsatellites). Starting from the genetic data, we performed two- and multipoint linkage analyses (both parametric and nonparametric) by means of Easy Linkage plus package (version 5.05). Results: The multipoint linkage analyses pointed out a region suggestive of linkage between the markers D12S310 and D12S364, at locus 12p12. In particular, we reached the best evidence of linkage performing multipoint analyses and assuming a recessive model, under the hypothesis of genetic heterogeneity (heterogeneity LOD score = 2.01 and α = 0.77). Conclusion: It is interesting to notice that the region at the marker D12S364 is located inside the gene coding for the glutamatergic receptor GRIN2B. Therefore, our finding not only confirmed the role of genetics in determining liability to bipolar disorder, but suggested glutamatergic transmission impairment as a possible cause. Nevertheless, we acknowledge that our study is heavily underpowered. Therefore, independent replication is needed.