Evidence of linkage and association on 18p11.2 for psychosis
2006
The genetic basis of bipolar disorder (BPD) and
schizophrenia (SCZ) has been established through numerous
clinical and molecular studies. Although often considered
separate nosological entities, evidence now suggests that the
two syndromes may share some genetic liability. Recent
studies have used a composite phenotype (psychosis) that
includes BPD, SCZ, psychosis not otherwise specified, and
schizoaffective disorder, to identify shared susceptibility
loci. Several chromosomal regions are reported to be shared
between these syndromes (18p, 6q, 10p, 13q, 22q). As a part
of our endeavor to scan these regions, we report a positive
linkage and association finding at 18p11.2 for psychosis.
Two-point linkage analysis performed on a series of 52
multiplex pedigrees with 23 polymorphic markers yielded a LOD
score of 2.02 at D18S37. An independent set of 159 parent
offspring trios was used to confirm this suggestive finding.
The TDT analysis yielded support for association between the
marker D18S453 and the disease allele (X 2 =4.829,
P<0.028). This region has been implicated by several
studies on BPD [Sjoholt et al. (2004); Mol Psychiatry
9(6):621-629; Washizuka et al. (2004); Biol Psychiatry
56(7):483-489; Pickard et al. (2005); Psychiatr Genet
15(1):37-44], SCZ [Kikuchi et al. (2003); J Med Dent Sci
50(3):225-229; Babovic-Vuksanovic et al. (2004); Am J Med
Genet 124(3):318-322] and also as a shared region between the
two diseases [Ishiguro et al. (2001); J Neural Transm
108(7):849-854; Reyes et al. (2002); Mol Psychiatry
7(4):337-339; Craddock et al. (2005); J Med Genet
42(3):193-204]. Our findings provide an independent
validation of the above reports, and suggest the presence of
susceptibility loci for psychoses in this region.
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