TY - JOUR
T1 - Support for a bipolar affective disorder susceptibility locus on chromosome 12q24.3
AU - Buttenschøn, Henriette Nørmølle
AU - Foldager, Leslie
AU - Zacharov, Tracey Flint
AU - Olsen, Inger Marie L
AU - Deleuran, Thomas
AU - Nyegaard, Mette
AU - Hansen, Mette M
AU - Kallunki, Pekka
AU - Christensen, Kenneth V
AU - Blackwood, Douglas H
AU - Muir, Walter J
AU - Straarup, Steen E
AU - Als, Thomas D
AU - Nordentoft, Merete
AU - Børglum, Anders
AU - Mors, Ole
PY - 2010
Y1 - 2010
N2 - 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. CONCLUSION: This study confirms 12q24.3 as a region of functional importance in the pathogenesis of BAD and highlights the importance of focused genotyping.
AB - 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. CONCLUSION: This study confirms 12q24.3 as a region of functional importance in the pathogenesis of BAD and highlights the importance of focused genotyping.
U2 - 10.1097/YPG.0b013e32833a2066
DO - 10.1097/YPG.0b013e32833a2066
M3 - Journal article
SN - 0955-8829
VL - 20
SP - 93
EP - 101
JO - Psychiatric Genetics
JF - Psychiatric Genetics
ER -