Searching susceptibility loci for bipolar disorder: a sib pair study on chromosome 12.
OBJECTIVE
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 alpha = 0.77).


CONCLUSIONS
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.
Lorenzi
Cristina
C
Genetic Laboratory, S. Raffaele Hospital, Vita-Salute University, Milan, Italy. lorenzi.cristina@hsr.it
Delmonte
Dario
D
Pirovano
Adele
A
Marino
Elena
E
Bongiorno
Fanny
F
Catalano
Marco
M
Colombo
Cristina
C
Bramanti
Placido
P
Smeraldi
Enrico
E
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D017422:Sequence Analysis, DNA; D035781:Siblings; D018709:Statistics, Nonparametric