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	Etain, B.,2006 PMID: 16534504
Citation	Etain, B., F. Mathieu, et al. (2006). "Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14." Mol Psychiatry 11(7): 685-694.
Disease Type	Bipolar I Disorder
Study Design	pedigree
Study Type	Genome-wide linkage study
Sample Size	87 sib-pairs from 70 nuclear families ascertained through an early-onset BPAD type I proband.
SNP/Region/Marker Size	384 microsatellite markers for whole genome wide
Predominant Ethnicity	Caucasian
Population	European
Gender	The sex (male/female) ratio was 0.66 for probands and 0.76 for siblings for the broad phenotype,the sex ratio was 0.80 for probands and 0.87 for siblings for the narrow phenotype.
Age Group	For the broad phenotype, mean AAO was 17.2,SD=2.4 years (range 11-21 years) for probands and 22.0,SD=6.8 years (range 9-46 years) for siblings.For the narrow phenotype, mean AAO was 17.4,SD=2.5 years (range 12-21 years) for probands and 17.5,SD= 2.9 years (range 9-21) for siblings.

Detail Info

Sample Diagnosis	DSM
Sample Status	In this study, patients suffering from recurrent major depressive episodes with age at onset below 21 years old were considered as affected, because it was postulated that they belong to the bipolar spectrum disorder as defined by Ghaemi et al. In addition, siblings of BPAD I early onset probands suffering from only one major depressive episode beginning before the age of 21 years old are known to be at high risk of progression to bipolar disorder. If parents were not evaluated, their phenotype was defined as unknown. Dizygotic and monozygotic twins were excluded. All subjects were of Caucasian origin. Seventy families were recruited as part of the European Collaborative Study of Early-Onset BPAD. Among these 70 families, 27 came from Germany (10 of these German families were included in a previous genome scan ), 16 from Ireland, 11 from France, 6 from Scotland, 6 from Switzerland and 4 from England. All probands were diagnosed with early-onset type I BPAD and were thus considered to be affected. For the sib-pair analysis, we defined two phenotypes. For the 'broad phenotype', siblings were considered as affected if they had BPAD type I or II or bipolar-type schizoaffective disorder, regardless of AAO, or if they had a major depressive episode (single or recurrent) with an AAO of 21 years or below. For the 'narrow phenotype', siblings were considered as affected if they suffered from BPAD type I with an AAO of 21 years or less, as for probands. The sample consisted of 87 sib-pairs according to the broad phenotype. Among them, 29 sib-pairs met the criteria for the narrow phenotype definition.
Technique	genotyping
Statistical Method	Non parametric bi-point and multipoint linkage analyses were performed using the NPL (Non Parametric Lodscore) statistic of the GENEHUNTER 2.1 program.
Result Summary	Non-parametric multipoint analysis suggested eight regions of linkage with P-values<0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide P-value estimated over 10 000 simulated replicates of 0.015 [0.01-0.02]). After genome-wide search analysis, we performed additional linkage analyses with increased marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non-parametric linkage score increased from 3.51 to 3.83. This study is the first to use early-onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families.

Regions reported by this study for BD (count: 19)

Region	Statistical Values	Author Comments	Result Category
10q23.33	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 0.5, P-value = 0.22; broad phenotype, NPL = 2.25, P-value = 0.01; Non parametric multipoint linkage analysis: narrow phenotype, NPL = 0.2, P-value > 0.05; broad phenotype, NPL = 2.45, P-value = 0.007	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
10q24.31	Non parametric bi-point linkage analysis: narrow phenotype, NPL = -0.06, P-value = 0.54; broad phenotype, NPL = 1.88, P-value = 0.03	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
16p13.2	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 1.26, P-value = 0.02; broad phenotype, NPL = 1.14, P-value = 0.12; Non parametric multipoint linkage analysis: narrow phenotype, NPL = 0.99, P-value > 0.05; broad phenotype, NPL = 1.7, P-value = 0.04	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
16q23.1	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 1.64, P-value = 0.004; broad phenotype, NPL = 1.36, P-value = 0.08; Non parametric multipoint linkage analysis: narrow phenotype, NPL = 1.64, P-value = 0.005; broad phenotype, NPL = 1.07, P-value = 0.14	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
10p13	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 1.07, P-value = 0.04; broad phenotype, NPL = 0.51, P-value = 0.3; Non parametric multipoint linkage analysis: narrow phenotype, NPL = 1.07, P-value = 0.04; broad phenotype, NPL = 0.43, P-value > 0.05	No Significant linkage was found in this region. No Significant linkage was found in this region.	Negative
2p21	Non parametric bi-point linkage analysis: For marker D2S2259, narrow phenotype, NPL = 0.69, P-value = 0.14; broad phenotype, NPL = 1.61, P-value = 0.05; For marker D2S391, narrow phenotype, NPL = 0.42, P-value = 0.25; broad phenotype, NPL = 1.94, P-value = 0.02	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
2p22.3	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 0.9, P-value = 0.08; broad phenotype, NPL = 1.7, P-value = 0.04	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
2p23.2	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 0.59, P-value = 0.17; broad phenotype, NPL = 1.67, P-value = 0.05	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
2q14.3	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 0.57, P-value = 0.18; broad phenotype, NPL = 1.65, P-value = 0.05; Non parametric multipoint linkage analysis: narrow phenotype, NPL = 0.48, P-value > 0.05; broad phenotype, NPL = 2.24, P-value = 0.01	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
17q11.2	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 1.17, P-value = 0.03; broad phenotype, NPL = 0.33, P-value = 0.37	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
17q21.32	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 0.97, P-value = 0.06; broad phenotype, NPL = 0.87, P-value = 0.19	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
17q22	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 1.01, P-value = 0.05; broad phenotype, NPL = 0.9, P-value = 0.18	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
20p12.2	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 0.3, P-value = 0.32; broad phenotype, NPL = 2.93, P-value = 0.002; Non parametric multipoint linkage analysis: narrow phenotype, NPL = 0.05, P-value > 0.05; broad phenotype, NPL = 2.25, P-value = 0.01	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7q36	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 0.12, P-value = 0.43; broad phenotype, NPL = 1.83, P-value = 0.03; Non parametric multipoint linkage analysis: narrow phenotype, NPL = 0.19, P-value > 0.05; broad phenotype, NPL = 2.43, P-value = 0.007	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7q21.3	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 0.62, P-value = 0.16; broad phenotype, NPL = 1.64, P-value = 0.05; Non parametric multipoint linkage analysis: narrow phenotype, NPL = 0.48, P-value > 0.05; broad phenotype, NPL = 1.49, P-value = 0.07	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
3p14.2	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 1.47, P-value = 0.01; broad phenotype, NPL = 2.88, P-value = 0.002; Non parametric multipoint linkage analysis: narrow phenotype, NPL = 1.65, P-value = 0.004; broad phenotype, NPL = 3.51, P-value = 0.0002	Significant linkage was found in this region. Significant linkage was found in this region.	Positive
3p14.1	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 0.46, P-value = 0.23; broad phenotype, NPL = 1.96, P-value = 0.02	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
5q32	Non parametric bi-point linkage analysis: D5S436, narrow phenotype, NPL = 1.1, P-value = 0.04; broad phenotype, NPL = 0.84, P-value = 0.2; Non parametric multipoint linkage analysis: D5S410, narrow phenotype, NPL = 1.37, P-value = 0.01; broad phenotype, NPL = 1.51, P-value = 0.06	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
4q13.3	Non parametric bi-point linkage analysis: narrow phenotype, NPL = 0.7, P-value = 0.14; broad phenotype, NPL = 1.68, P-value = 0.04; Non parametric multipoint linkage analysis: narrow phenotype, NPL = 0.81, P-value > 0.05; broad phenotype, NPL = 1.73, P-value = 0.04	No significant linkage was found in this region. No significant linkage was found in this region.	Negative