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	McAuley, E. Z.,2009 PMID: 18227837
Citation	McAuley, E. Z., I. P. Blair, et al. (2009). "A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26." Mol Psychiatry 14(5): 492-500.
Disease Type	Bipolar Disorder
Study Design	pedigree
Study Type	Genome-wide linkage study
Sample Size	35-pedigree cohort
SNP/Region/Marker Size	400 microsatellite markers for whole genome wide
Predominant Ethnicity
Population	Australian

Detail Info

Sample Diagnosis	RDC
Sample Status	The families were ascertained as part of an ongoing bipolar genetics study by the Mood Disorders Unit,Prince of Wales Hospital/School of Psychiatry,University of New South Wales, Sydney, Australia.Blood was collected from 288 available individuals,of whom 130 were affected (according to the broad disease definition described below), and DNA was extracted using standard methods. In total there were 56 individuals diagnosed with BPI (BPI) disorder,12 with schizoaffective disorder manic type (SZ/MA),22 with BPII (BPII) disorder and 40 with recurrent unipolar depression. The average number of genotyped individuals in a pedigree was eight and the average number of genotyped affected individuals(BPI, SZ/MA, BPII or unipolar depression) was four per pedigree.
Technique	genotyping
Statistical Method	Two-point linkage analyses and multipoint genetic linkage analysis were performed using the MLINK computer program of the LINKAGE 5.2 package.
Result Summary	We report the results of a genome-wide linkage analysis conducted on a cohort of 35 Australian bipolar disorder families which identified evidence of significant linkage on chromosome 15q25-26 and suggestive evidence of linkage on chromosomes 4q, 6q and 13q. Subsequent fine-mapping of the chromosome 15q markers, using allele frequencies calculated from our cohort, gave significant results with a maximum two-point LOD score of 3.38 and multipoint LOD score of 4.58 for marker D15S130. Haplotype analysis based on pedigree-specific, identical-by-descent allele sharing, supported the location of a bipolar susceptibility gene within the Z(max-1) linkage confidence interval of 17 cM, or 6.2 Mb, between markers D15S979 and D15S816. Non-parametric and affecteds-only linkage analysis further verified the linkage signal in this region. A maximum NPL score of 3.38 (P=0.0008) obtained at 107.16 cM (near D15S130), and a maximum two-point LOD score of 2.97 obtained at marker D15S1004 (affecteds only), support the original genome-wide findings on chromosome 15q. These results are consistent with four independent positive linkage studies of mood and psychotic disorders, and raise the possibility that a common gene for susceptibility to bipolar disorder, and other psychiatric disorders may lie in this chromosome 15q25-26 region.

Regions reported by this study for BD (count: 9)

Region	Statistical Values	Author Comments	Result Category
13q22.1	Two-point linkage analysis: Maximum LOD score = 2.39, 0.6dominant, Model III	There is a trend for Significant linkage. There is a trend for Significant linkage.	Trend
13q32.2	Two-point linkage analysis: Maximum LOD score = 1.93, 0.6dominant, Model III	There is a trend for Significant linkage. There is a trend for Significant linkage.	Trend
4q21.23	Two-point linkage analysis: Maximum LOD score = 2, 0.6recessive, Model II	There is a trend for Significant linkage. There is a trend for Significant linkage.	Trend
15q26.2	Two-point linkage analysis: Maximum LOD score = 3.87, 0.6dominant, Model III	Significant linkage was found in this region. Significant linkage was found in this region.	Positive
15q26.1	Two-point linkage analysis: Maximum LOD score = 2.12, 0.6dominant, Model III	There is a trend for Significant linkage. There is a trend for Significant linkage.	Trend
15q25-26	Two-point linkage analysis: For marker D15S130, LOD score = 3.38	Significant linkage was found in this region. Significant linkage was found in this region.	Positive
6q27	Two-point linkage analysis: Maximum LOD score = 2.89, 0.6recessive, Model III	There is a trend for Significant linkage. There is a trend for Significant linkage.	Trend
6q25.3	Two-point linkage analysis: Maximum LOD score = 2.65, 0.6recessive, Model III	There is a trend for Significant linkage. There is a trend for Significant linkage.	Trend
4q34.3	Two-point linkage analysis: Maximum LOD score = 2.31, 0.9dominant, Model II	There is a trend for Significant linkage. There is a trend for Significant linkage.	Trend