BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Basic Info

Reference	Badenhop, R. F., 2001 PMID: 11443523
Citation	Badenhop, R. F., M. J. Moses, et al. (2001). "A genome screen of a large bipolar affective disorder pedigree supports evidence for a susceptibility locus on chromosome 13q." Mol Psychiatry 6(4): 396-403.
Disease Type	Bipolar Disorder
Study Design	pedigree
Study Type	Genome-wide linkage study
Sample Size	40 individuals, including six affecteds
SNP/Region/Marker Size	a 10 cM genome screen using 400 microsatellite markers
Predominant Ethnicity	Caucasian
Population	Australian

Detail Info

Sample Diagnosis	RDC
Sample Status	Family ascertainment The family was ascertained as part of an ongoing bipolar genetics study via the Mood Disorders Unit, Prince of Wales Hospital/University of New South Wales, Sydney, Australia. Medium to large multigenerational pedigrees were recruited, with illness over at least two generations and containing a minimum of three affected individuals, two of whom were diagnosed with bipolar I. Families were Caucasian and almost entirely of British descent. The family used in this study contained 58 individuals with 40 available for analysis which included six affecteds; four with bipolar I (BPI) and two with recurrent unipolar depression (UP) (Figure 1). Simulation analyses using SLINK and MSIM24,25 were carried out in order to determine the power of this pedigree to detect linkage. Using a dominant model of inheritance with 90% maximum age-specific penetrance, a 6-allele marker and including BPI and UP individuals as affected, the maximum expected LOD scores for this pedigree under the assumption of linkage and no linkage were 3.5 and 0.29, respectively.
Technique	genotyping
Statistical Method	The ANALYZE package26 was used to automate twopoint LOD score analysis. Parametric multipoint analysis was performed using LINKMAP of the LINKAGE Package, version 5.2.27 Non-parametric multipoint analyses were performed using GENEHUNTER.Two disease thresholds were used in the analysis. In the narrow disease model, individuals diagnosed with BPI were classified as affected and all other family members were classified as unaffected. In the broad disease model, individuals diagnosed with either BPI or UP were classified as affected and all other family members were considered unaffected.
Result Summary	We found strongest evidence for linkage to chromosome 13q14. A maximum NPL score of 4.09 (P = 0.008) was obtained between markers D13S1272 and D13S153 using GENEHUNTER. A maximum two-point LOD score of 2.91 (theta = 0.0) was found for marker D13S153 and a maximum three-point LOD score of 3.0 was obtained between markers D13S291 and D13S153 under a recessive model with 90% maximum age-specific penetrance and including bipolar I and unipolar individuals as affected. Several other markers in the region, D13S175, D13S218, D13S263, and D13S156 had two-point LOD scores greater than 1.5. These results meet the criteria for evidence of suggestive linkage. Haplotype analysis enabled us to narrow the likely disease region to a 6 cM region between markers D13S1272 and D13S1319, which contains the serotonin 2A receptor candidate gene. Two single nucleotide polymorphisms were identified in this gene but we did not detect any significant differences in allele frequency in a case-control sample. The region on chromosome 13q14-32 has previously been implicated in other bipolar and schizophrenia cohorts. Our results provide further support for the existence of a susceptibility locus on chromosome 13q14.

Regions reported by this study for BD (count: 5)

Region	Statistical Values	Author Comments	Result Category
13q11	Linkage analysis: Two-point LOD = 1.55, 90%recessive, broad disease	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
13q13	Linkage analysis: Two-point LOD = 2.07, 90%recessive, broad disease	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
13q14	Linkage analysis: Two-point LOD = 2.91, 90%recessive, broad disease	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
13q21	Linkage analysis: Two-point LOD = 1.53, 90%recessive, broad disease	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
3q21	Linkage analysis: Two-point LOD = 1.55, 60%dominant, narrow disease	No significant linkage was found in this region. No significant linkage was found in this region.	Negative