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	Jasinska, A. J.,2009 PMID: 19319892
Citation	Jasinska, A. J., S. Service, et al. (2009). "A narrow and highly significant linkage signal for severe bipolar disorder in the chromosome 5q33 region in Latin American pedigrees." Am J Med Genet B Neuropsychiatr Genet 150B(7): 998-1006.
Disease Type	Bipolar I Disorder
Study Design	pedigree and family-based
Study Type	Candidate-region linkage study and candidate-gene association study
Sample Size	249 patients from CVCR and 110 patients from CO
SNP/Region/Marker Size	1134 SNPs in an approximately 9Mb region
Predominant Ethnicity
Population	Latin American

Detail Info

Sample Status	Pedigree samples used in this study come from three large families from the CVCR and 14 intermediate size pedigrees from CO. Extensive genealogic information documents the descent of most individuals in these pedigrees form the CVCR and CO founding populations. The average pedigree size was 16 persons (ranging from 6 to 41), with an average of five BP-I affected individuals per pedigree (ranging from 2 to 13). The largest CVCR pedigree, CR201, includes 25 individuals diagnosed with BP-I [Service et al., 2006b]. Two other CVCR pedigrees, CR001 and CR004, are related by several inbreeding loops and altogether include 30 individuals affected with BP-I [Freimer et al., 1996]. The CO pedigrees contain 3-13 BP-I cases per family and altogether include 85 BP-I patients [Herzberg et al., 2006]. The sample for association analyses comprised independently ascertained BP-I affected subjects and their parent(s). These individuals were recruited, without consideration of family history of psychiatric disorders, from patients admitted with a diagnosis of BP-I to psychiatric hospitals in CVCR and CO. A total of 249 patients from CVCR and 110 patients from CO met these criteria. In the CVCR sample set, 101 patients had both parents available for genotyping (trios), and 148 had only one parent available for genotyping (duos). The CO sample set consisted of 54 trios and 56 duos available for genotyping.
Technique	genotyping
Statistical Method	Two-point parametric linkage analysis in the pedigree samples was performed using the linkage option in Mendel [Lange et al., 2001].Association analysis suitable for the pedigrees was conducted using the association given linkage option in Mendel [Cantor et al.,2005] using the same allele frequency estimates as for linkage analysis.A two-point test of association was performed using Transmit[Clayton, 1999] for both duos and trios. As a test of association in the Transmit analysis, we used the asymptotic chi-squared test.
Result Summary	Combining pedigrees from CVCR and CO yields a LOD score of 4.9 at SNP rs10035961. Two other SNPs (rs7721142 and rs1422795) within the same 94 kb region also displayed LOD scores greater than 4. This linkage peak coincides with our prior microsatellite results and suggests a narrowed BP-I susceptibility regions in these families. To investigate if the locus implicated in the familial form of BP-I also contributes to disease risk in the population, we followed up the family results with association analysis in duo and trio samples, obtaining signals within 2 Mb of the peak linkage signal in the pedigrees; rs12523547 and rs267015 (P = 0.00004 and 0.00016, respectively) in the CO sample and rs244960 in the CVCR sample and the combined sample, with P = 0.00032 and 0.00016, respectively. It remains unclear whether these association results reflect the same locus contributing to BP susceptibility within the extended pedigrees.

Regions reported by this study for BD (count: 1)

Region	Statistical Values	Author Comments	Result Category
5q33	Two-Point Parametric LOD score: For marker rs6863955, 0.4 for CVCR sample, 3.28 for CO sample, 1.78 for combined sample; For marker rs253602, 3.37 for CVCR sample, 0.57 for CO sample, 2.99 for combined sample; For marker rs7713029, 1.72 for CVCR sample, 1.72 for CO sample, 3.27 for combined sample; For marker rs10036026, 0.17 for CVCR sample, 3.29 for CO sample, 2.37 for combined sample; For marker rs9313827, 0.17 for CVCR sample, 3.29 for CO sample, 2.38 for combined sample; For marker rs2176297, 1.18 for CVCR sample, 2.19 for CO sample, 3.33 for combined sample	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend