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	Ekholm, J. M.,2003 PMID: 12874110
Citation	Ekholm, J. M., T. Kieseppa, et al. (2003). "Evidence of susceptibility loci on 4q32 and 16p12 for bipolar disorder." Hum Mol Genet 12(15): 1907-1915.
Disease Type	Bipolar Disorder
Study Design	pedigree
Study Type	Genome-wide linkage study
Sample Size	41 families with at least two affected siblings
SNP/Region/Marker Size	389 microsatellite markers for whole genome wide
Predominant Ethnicity	Caucasian
Population	Finnish

Detail Info

Sample Diagnosis	DSM
Sample Status	The detailed ascertainment strategy is described elsewhere (28). Briefly, prior to ascertainment, two hierarchical diagnostic categorieswere formed: (i) BPD-I and SA-BPD; and (ii) BPD-II, bipolar NOS, cyclothymic disorder and rMDD.With permission from the Ministry of Social Affairs and Health, national medical registers were used to collect all bipolar families nationwide that included at least two subjects diagnosed with diagnostic category I. Two psychiatrists, unaware of the family relationships, made independent diagnoses of the subjects based on all available case notes according to DSM-IV diagnostic criteria. Altogether, 41 Finnish bipolar families, of which four were extended, were analyzed in this study.
Technique	genotyping
Statistical Method	In the first stage of the genome-wide scan the preferred primary analyses methods were two-point linkage analyses with locus homogeneity, which were carried out using the MLINK program from FASTLINK 4.1P package (54), as well as locus heterogeneity using the HOMOG program (55). In addition two-point non-parametric statistics were also calculated by adopting the ASP analysis.In the fine mapping stage the association analyses and three-point analyses were performed for these selected regions.The association analyses were performed using the PSEUDOMARKER program (57), which is a linkage analysis software for joint linkage and/or linkage disequilibrium analysis.
Result Summary	We identified one distinct locus on 16p12 providing significant evidence for linkage in two-point analysis (Z(max)=3.4). Furthermore, three loci with a two-point LOD score >2.0 were observed with markers on 4q32, 12q23 and Xq25, the latter locus having been earlier identified in one extended Finnish pedigree. In the second stage we fine mapped these chromosomal regions and also genotyped additional family members. In the fine mapping stage, 4q32 provided significant evidence of linkage for the three-point analyses (Z(max)=3.6) and 16p12 produced a three-point LOD score of 2.7. Since the identified chromosomal regions replicate earlier linkage findings in either bipolar disorder or other mental disorders, they should be considered good targets for further genetic analyses.

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

Region	Statistical Values	Author Comments	Result Category
Chr 16_52.26cM	Linkage analysis: Model: Dom, Broad, Two-point LOD score = 0.8	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 4_155.19cM	Linkage analysis: Model: ASP, Narrow, Two-point LOD score = 0.9	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 4_161.91cM	Linkage analysis: Model: Rec, Broad, Two-point LOD score = 1.9	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
4q32	Linkage analysis: Model: Dom, Broad, Two-point LOD score = 2.6	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
Chr 12_107.86cM	Linkage analysis: Model: Dom, Narrow, Two-point LOD score = 0.5(theta = 0.24)	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 12_111.87cM	Linkage analysis: Model: Dom, Narrow, Two-point LOD score = 0.4(theta = 0.22)	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
Chr 16_46.94cM	Linkage analysis: Model: Dom, Broad, Two-point LOD score = 0.4	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
16p12	Linkage analysis: Model: Dom, Narrow, Two-point LOD score = 3.4(theta = 0.22)	Significant linkage was found in this region(P-value < 0.05)...... Significant linkage was found in this region(P-value < 0.05). More...	Positive
12q23	Linkage analysis: Model: ASP, Broad, Two-point LOD score = 2	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend