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	Fullerton, J. M.,2010 PMID: 20022591
Citation	Fullerton, J. M., J. A. Donald, et al. (2010). "Two-dimensional genome scan identifies multiple genetic interactions in bipolar affective disorder." Biol Psychiatry 67(5): 478-486.
Disease Type	Bipolar Disorder
Study Design	pedigree and case-control
Study Type	Genome-wide linkage study and genetic interaction study
Sample Size	65 Australian extended pedigrees containing 643 genotyped individuals (of whom 40% were diagnosed with affective disorder);WTCCC and GAIN datasets: 2933 bipolar disorder (and related disorder) cases and 2534 control subjects.
SNP/Region/Marker Size	391 microsatellite polymorphic markers for whole genome wide
Predominant Ethnicity
Population	Australian,WTCCC collections and GAIN collections

Detail Info

Sample Diagnosis	RDC
Sample Status	Pedigrees have been collected through the Mood Disorders Unit and Black Dog Institute at the Prince of Wales Hospital and the School of Psychiatry, University of New South Wales, Sydney, Australia.Using the broad phenotypic definition of bipolar disorder, 285 individuals were considered affected(of whom 260 had consented to DNA collection): 133 with bipolar I disorder (BPI), 30 with bipolar II disorder (BPII), 30 with schizoaffective disorder manic type (SZ/MA), and 92 with recurrent unipolar major depression (UP); 381 individuals were not affected. The average pedigree size was reduced from 16 to 12.5 after pruning, with an average of 9.9 genotyped individuals of whom 4.4 individuals had a diagnosis of affective disorder.
Technique	genotyping
Statistical Method	Univariate Nonparametric Linkage Scan:Single-point nonparametric (model-free) linkage (NPL) analysis was performed across all autosomes and chromosome X with MERLIN using the Kong and Cox linear model and computing allele sharing using the Whittemore and Halpern S-all and S-pairs statistics.Analysis of Microsatellite Interaction:We used the NPL-based method of Cox et al. described by Sullivan et al.in their study on nicotine dependence,which used correlations in family-specific linkage scores to detect evidence of genetic interaction.Interaction-Specific Linkage Analysis:Regions implicated through the correlation analysis were subject to an interaction-specific linkage analysis in ALLEGRO(http://www.decode.com/software) to determine the robustness of linkage interdependence.
Result Summary	RESULTS: Significant NPL peaks were detected on chromosomes 2q24-33, 7q21-31, and 17q11-25 (Z = 3.12, 3.01, and 2.95 respectively), with four additional suggestive peaks identified. Four robust interchromosomal interaction clusters exceeding Bonferroni correction at alpha = .05 (uncorrected p < 5.38e-07) were detected on 11q23-25-2p15-12, 4q32-35-1p36, 12q23-24-4p16-15, and 20q13-9q21-22. This linkage interdependence was determined significant after permutation analysis (p = .002-.0002). A suggestive interaction was observed in the combined data on 2p14-11q23 (uncorrected p = 5.76E-10, Bonferroni corrected p = .068). CONCLUSIONS: This study indicates a complex interplay between multiple loci underlying bipolar disorder susceptibility, and highlights the continuing usefulness of extended pedigrees in complex genetics. The challenge lies in the identification of specific gene interactions and their biological validation.

Haplotypes reported by this study for BD (count: 4)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
D20S196 - D9S167		20q13, 9q21	Interaction-Specific Linkage:at Marker D20S196, equal NPL-pair=1.5602, interacting locus NPL-pairs=2.4261, permuted P-value = 0.0004; at Marker D9S167, equal NPL-pair=0.0623, interacting locus NPL-pairs=2.3812, permuted P-value = 0.0004	No positive linkage was found in this region(significant:NPL...... No positive linkage was found in this region(significant:NPL=2.8, suggestive:NPL=2.5). More...	Negative
D2S337 - D11S925		2p14, 11q23	Interaction-Specific Linkage:at Marker D2S337, equal NPL-pair=0.5866, interacting locus NPL-pairs=2.202, permuted P-value = 0.0005; at Marker D11S925, equal NPL-pair=1.9459, interacting locus NPL-pairs=2.9547, permuted P-value = 0.002	Positive linkage was found in this region.(significant:NPL=2...... Positive linkage was found in this region.(significant:NPL=2.8, suggestive:NPL=2.5) More...	Positive
D4S419 - D12S78		4q15, 12q21	Interaction-Specific Linkage:at Marker D4S419, equal NPL-pair=0.8546, interacting locus NPL-pairs=3.1641, permuted P-value = -0.0002; at Marker D12S78, equal NPL-pair=1.1055, interacting locus NPL-pairs=2.449, permuted P-value = -0.0002	Positive linkage was found in this region.(significant:NPL=2...... Positive linkage was found in this region.(significant:NPL=2.8, suggestive:NPL=2.5) More...	Positive
D4S1597 - D1S468		4q35, 1p36	Interaction-Specific Linkage:at Marker D4S1597, equal NPL-pair=2.3352, interacting locus NPL-pairs=3.2785, permuted P-value = 0.0003; at Marker D1S468, equal NPL-pair=0.4511, interacting locus NPL-pairs=1.7052, permuted P-value = 0.003	Positive linkage was found in this region.(significant:NPL=2...... Positive linkage was found in this region.(significant:NPL=2.8, suggestive:NPL=2.5) More...	Positive

Regions reported by this study for BD (count: 7)

Region	Statistical Values	Author Comments	Result Category
19p13-q13	Univariate Nonparametric Linkage Analysis: Zmax (S-ALL) = 2.71, Zmax (S-PAIRS) = 2.25, Empirical P-value (S-ALL) = 0.005	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
2q24-33	Univariate Nonparametric Linkage Analysis: Zmax (S-ALL) = 3.12, Zmax (S-PAIRS) = 3.04, Empirical P-value (S-ALL) = 0.001	Significant linkage was found in this region. Significant linkage was found in this region.	Positive
4q31-35	Univariate Nonparametric Linkage Analysis: Zmax (S-ALL) = 2.75, Zmax (S-PAIRS) = 3.12, Empirical P-value (S-ALL) = 0.003	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
7q21-31	Univariate Nonparametric Linkage Analysis: Zmax (S-ALL) = 3.01, Zmax (S-PAIRS) = 2.76, Empirical P-value (S-ALL) = 0.002	Significant linkage was found in this region. Significant linkage was found in this region.	Positive
13q12-14	Univariate Nonparametric Linkage Analysis: Zmax (S-ALL) = 2.7, Zmax (S-PAIRS) = 2.98, Empirical P-value (S-ALL) = 0.004	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
17q11-25	Univariate Nonparametric Linkage Analysis: Zmax (S-ALL) = 2.95, Zmax (S-PAIRS) = 2.99, Empirical P-value (S-ALL) = 0.004	Significant linkage was found in this region. Significant linkage was found in this region.	Positive
9q21-32	Univariate Nonparametric Linkage Analysis: Zmax (S-ALL) = 2.61, Zmax (S-PAIRS) = 1.95, Empirical P-value (S-ALL) = 0.005	No significant linkage was found in this region. No significant linkage was found in this region.	Negative