Support for a bipolar affective disorder susceptibility locus on chromosome 12q24.3.
OBJECTIVE
Linkage and association studies of bipolar affective disorder (BAD) point out chromosome 12q24 as a region of interest.


METHODS
To investigate this region further, we conducted an association study of 22 DNA markers within a 1.14 Mb region in a Danish sample of 166 patients with BAD and 311 control individuals. Two-hundred and four Danish patients with schizophrenia were also included in the study.


RESULTS
We observed highly significant allelic and genotypic association between BAD and two highly correlated markers. The risk allele of both markers considered separately conferred an odds ratio of 2 to an individual carrying one risk allele and an odds ratio of 4 for individuals carrying both risk alleles assuming an additive genetic model. These findings were supported by the haplotype analysis. In addition, we obtained a replication of four markers associated with BAD in an earlier UK study. The most significantly associated marker was also analyzed in a Scottish case-control sample and was earlier associated with BAD in the UK cohort. The association of that particular marker was strongly associated with BAD in a meta-analysis of the Danish, Scottish and UK sample (P=0.0003). The chromosome region confined by our most distant markers is gene-poor and harbours only a few predicted genes. This study implicates the Slynar locus. We confirmed one annotated Slynar transcript and identified a novel transcript in human brain cDNA.


CONCLUSIONS
This study confirms 12q24.3 as a region of functional importance in the pathogenesis of BAD and highlights the importance of focused genotyping.
Buttenschøn
Henriette Nørmølle
HN
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark. henrbutt@rm.dk
Buttenchøn
Henriette Nørmølle
HN
Foldager
Leslie
L
Flint
Tracey J
TJ
Olsen
Inger Marie L
IM
Deleuran
Thomas
T
Nyegaard
Mette
M
Hansen
Mette M
MM
Kallunki
Pekka
P
Christensen
Kenneth V
KV
Blackwood
Douglas H
DH
Muir
Walter J
WJ
Straarup
Steen E
SE
Als
Thomas D
TD
Nordentoft
Merete
M
Børglum
Anders D
AD
Mors
Ole
O
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003718:Denmark; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics
D005819:Genetic Markers; D012333:RNA, Messenger