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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Study Report

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Basic Info

Reference	Liu, J.,2003 PMID: 12660806
Citation	Liu, J., S. H. Juo, et al. (2003). "Evidence for a putative bipolar disorder locus on 2p13-16 and other potential loci on 4q31, 7q34, 8q13, 9q31, 10q21-24, 13q32, 14q21 and 17q11-12." Mol Psychiatry 8(3): 333-342.
Disease Type	Bipolar Disorder
Study Design	pedigree
Study Type	Genome-wide linkage study
Sample Size	373 individuals in 40 pedigrees
SNP/Region/Marker Size	343 microsatellite markers for whole genome wide
Predominant Ethnicity	Caucasian
Population	American and Israeli
Age Group	Adults

Detail Info

Sample Diagnosis	RDC
Sample Status	A detailed description of the pedigree set, including ascertainment, diagnostic procedures and affection status models, is given elsewhere.23 Briefly, our overall sample consists of 1508 individuals (Caucasian, age 16 or over) in 57 extended pedigrees with high density of BP. We required at least two members per pedigree (including the proband) with a lifetime diagnosis of mania (BPI or schizoaffective disordermanic type; the BPI category comprised nearly 90% of manic syndromes in this sample, with schizoaffective disorder accounting for a mere 10%). The pedigrees were obtained in the US (39 pedigrees) and Israel (18 pedigrees) using the same research protocol. US and Israeli pedigrees displayed similar rates of BP and related mood disorders.To address the question of phenotypic uncertainty, we used several affection status definitions, or diagnostic models. The 'affected' category was broadened progressively from narrow to broader phenotypic boundaries using three diagnostic models. BP1: manic syndrome, mostly BPI; BP2: same as BP1 plus BPII; BP3: same as BP2 plus recurrent major depressive disorder (MDD) (including some cases of recurrent schizoaffective, mainly affective-depressed only). These disorders aggregate in families of bipolar probands and are therefore considered part of the bipolar 'spectrum'. BP1 represents the 'core' phenotype (narrowest disease definition), with the highest relative risk.The genotyped subset thus created consisted of 373 individuals from the 40 most informative pedigrees, 307 of whom were affected (an average of seven or eight affected individuals per pedigree). The distribution of diagnoses was as follows: 119 individuals with BPI, 90 with BPII and 98 with recurrent MDD.
Technique	genotyping
Statistical Method	Two-point parametric analysis was carried out using the MLINK program from the FASTLINK package.Multipoint analyses were conducted using the same analytical model that was used to produce the two-point results.Affected sib-pair (ASP) analysis was performed using version (2.0) of MAPMAKER/SIBS,which uses the maximum-likelihood score (MLS) approach.
Result Summary	This analysis yielded significant evidence of linkage (genome-wide P&<0.05) for markers on 2p13-16. Standard linkage analysis was also supportive of linkage to 2p13-16 (lod=3.20), and identified several other interesting regions: 4q31 (lod=3.16), 7q34 (lod=2.78), 8q13 (lod=2.06), 9q31 (lod=2.07), 10q24 (lod=2.79), 13q32 (lod=2.2), 14q21 (lod=2.36) and 17q11-12 (lod=2.75). In this systematic, large-scale study, we identified novel putative loci for BP (on 2p13-16, 8q13 and 14q21) and found support for previously proposed loci (on 4q31, 7q34, 9q31, 10q21-24, 13q32 and 17q11-12). Two of the regions implicated in our study, 2p13-14 and 13q32, have also been linked to schizophrenia, suggesting that the two disorders may have susceptibility genes in common.

Regions reported by this study for BD (count: 18)

Region	Statistical Values	Author Comments	Result Category
9q21-22	Multipoint ASP results: LOD = 1.4, Model BP1	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
8q13	Two-point parametric linkage results: Maximum LOD = 1.86, Model BP2, Dominant, theta = 0.25	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
9q31	Two-point parametric linkage results: Maximum LOD = 1.88, Model BP1, Dominant, theta = 0	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
10q21	Two-point parametric linkage results: Maximum LOD = 1.99, Model BP2, Dominant, theta = 0.2	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
10q24	Two-point parametric linkage results: Maximum LOD = 2.79, Model BP1, Dominant, theta = 0	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
11p15	Multipoint ASP results: LOD = 1.44, Model BP3	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
13q32	Multipoint ASP results: LOD = 2.2, Model BP2	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
14q21	Multipoint ASP results: LOD = 2.36, Model BP2	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
14q32	Multipoint ASP results: LOD = 1.36, Model BP1	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
17q11-12	Two-point parametric linkage results: Maximum LOD = 2.68, Model BP1, Dominant, theta = 0.15	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
18q12-21	Multipoint ASP results: LOD = 1.18, Model BP1	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
1p36	Multipoint ASP results: LOD = 1.71, Model BP3	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
2p13-16	Multipoint ASP results: LOD = 1.59, Model BP2; Two-point parametric linkage results: Maximum LOD = 3.2, Model BP2, Dominant, theta = 0	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
3q27-28	Two-point parametric linkage results: Maximum LOD = 1.89, Model BP1, Recessive, theta = 0.15	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
4q31	Two-point parametric linkage results: Maximum LOD = 3.16, Model BP3, Dominant, theta = 0.15	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
7q31-33	Multipoint ASP results: LOD = 1.12, Model BP3	No significant linkage was found in this region. No significant linkage was found in this region.	Negative
7q34	Multipoint ASP results: LOD = 2.78, Model BP2	Suggestive linkage was found in this region. Suggestive linkage was found in this region.	Trend
8p23	Multipoint ASP results: LOD = 1.77, Model BP2	No significant linkage was found in this region. No significant linkage was found in this region.	Negative