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	Avramopoulos, D., 2007 PMID: 18007143
Citation	Avramopoulos, D., V. K. Lasseter, et al. (2007). "Stage II follow-up on a linkage scan for bipolar disorder in the Ashkenazim provides suggestive evidence for chromosome 12p and the GRIN2B gene." Genet Med 9(11): 745-751.
Disease Type	Bipolar Disorder
Study Design	pedigree
Study Type	Candidate-region linkage study
Sample Size	41 families (182 subjects with DNA available)
SNP/Region/Marker Size	145 variants
Predominant Ethnicity
Population	Ashkenazi
Gender	46% male
Age Group	pedigree : 5-76 (mean age=25.5) years for all affected individuals

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	Among the total set of 41 families, BPI (76.3%), BPII (23.7%); the average age at onset among the 22 families in the BPI subset was 24.7 years (range, 14-69 years); in the larger data set of 41 pedigrees, 34 individuals were classified as 'phenotype unknown' in all analyses: major depression without comorbid anxiety disorders (n=17), major depression with comorbid anxiety disorders (n=6), cyclothymia (n=1), possible BPII (n=3), schizophrenia/schizoaffective disorder (n=6), or schizophrenia spectrum personality disorder (n=1).
Technique	Polymerase chain reaction (PCR) amplifications were set up on Zymark ALH 400 (Zymark Corp., Hopkinton, MA), run on MJR Tetrad thermal cycler (Bio-Rad Laboratories, Inc., Waltham,MA) and pooled on Gilson Cyberlab C200 robots (Gilson, Inc., Middleton, WI). The PCR products were supplemented with the internal size standard GS500-LIZ (Applera Corp.), and the pools were separated and detected on ABI-3730 Sequencers (Applera Corp.).
Statistical Method	Mendelian errors were identified using the PedCheck and GENEHUNTER analysis software, and GENEHUNTER was also used to identify markers showing recombination with both their flanking markers. Allele frequencies were estimated from the parental genotypes and linkage analyses were performed using GENEHUNTER.
Result Summary	They saw an improvement of the evidence for linkage in most regions, with the most notable change on chromosome 12p13.1-p12.3, where the evidence of linkage is now suggestive. This region harbors the gene encoding the ionotropic glutamate receptor subunit 2B (GRIN2B), a gene that previously yielded evidence for association in a candidate gene study on 323 Ashkenazi Jewish bipolar case-parent trios. They find that the evidence for linkage is significantly correlated with the presence of the putative high-risk allele identified in their candidate gene study. Following up weaker signals can significantly improve linkage signals even after relatively small increases in information content. Their results on chromosome 12p support GRIN2B as a candidate gene for bipolar disorder that needs further investigation.

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

Region	Statistical Values	Author Comments	Result Category
Chr 2	P-value = 0.021, NPL = 2.05, Dominant Max HLOD = 1.43, Recessive Max HLOD = 0.46 in Ashkenazi pedigrees; P-value = 0.03, NPL = 1.9, Dominant Max HLOD = 0.58, Recessive Max HLOD = 0.96 in BPI-restricted pedigrees	the absolute value of the resulting scores remained moderate the absolute value of the resulting scores remained moderate	Negative
Chr 4	P-value = 0.02, NPL = 2.06, Dominant Max HLOD = 0.86, Recessive Max HLOD = 1.07 in Ashkenazi pedigrees; P-value = 0.033, NPL = 1.86, Dominant Max HLOD = 0.341, Recessive Max HLOD = 0.375 in BPI-restricted pedigrees	the absolute value of the resulting scores remained moderate the absolute value of the resulting scores remained moderate	Negative
Chr 6	P-value = 0.025, NPL = 1.97, Dominant Max HLOD = 1.17, Recessive Max HLOD = 0.51 in Ashkenazi pedigrees; P-value = 0.06, NPL = 1.57, Dominant Max HLOD = 0.83, Recessive Max HLOD = 0.821 in BPI-restricted pedigrees	the absolute value of the resulting scores remained moderate the absolute value of the resulting scores remained moderate	Negative
Chr 7	P-value = 0.028, NPL = 1.91, Dominant Max HLOD = 0.19, Recessive Max HLOD = 0.53 in Ashkenazi pedigrees; P-value = 0.037, NPL = 1.81, Dominant Max HLOD = 0.45, Recessive Max HLOD = 0.6 in BPI-restricted pedigrees	the absolute value of the resulting scores remained moderate the absolute value of the resulting scores remained moderate	Negative
Chr 9	P-value = 0.035, NPL = 1.82, Dominant Max HLOD = 0.87, Recessive Max HLOD = 1.23 in Ashkenazi pedigrees; P-value = 0.069, NPL = 1.5, Dominant Max HLOD = 0.52, Recessive Max HLOD = 0.88 in BPI-restricted pedigrees	the absolute value of the resulting scores remained moderate the absolute value of the resulting scores remained moderate	Negative
Chr 12	P-value = 0.04, NPL = 1.8, Dominant Max HLOD = 0.8, Recessive Max HLOD = 0.84 in Ashkenazi pedigrees; P-value = 0.009, NPL = 2.42, Dominant Max HLOD = 1.14, Recessive Max HLOD = 2.05 in BPI-restricted pedigrees	this region was elevated into a 'suggestive' result by stand...... this region was elevated into a 'suggestive' result by standard criteria; the CC genotype showed increased evidence of linkage, but GIST analysis did not achieve statistical significance More...	Negative
Chr 14	P-value = 0.07, NPL = 1.47, Dominant Max HLOD = 0.49, Recessive Max HLOD = 0.68 in Ashkenazi pedigrees; P-value = 0.06, NPL = 1.57, Dominant Max HLOD = 0.52, Recessive Max HLOD = 0.89 in BPI-restricted pedigrees	the absolute value of the resulting scores remained moderate the absolute value of the resulting scores remained moderate	Negative
Chr 16	P-value = 0.07, NPL = 1.47, Dominant Max HLOD = 0.23, Recessive Max HLOD = 0.73 in Ashkenazi pedigrees; P-value = 0.03, NPL = 1.96, Dominant Max HLOD = 0.55, Recessive Max HLOD = 0.67 in BPI-restricted pedigrees	the absolute value of the resulting scores remained moderate the absolute value of the resulting scores remained moderate	Negative
Chr 19	P-value = 0.1, NPL = 1.27, Dominant Max HLOD = 0.55, Recessive Max HLOD = 0.09 in Ashkenazi pedigrees; P-value = 0.025, NPL = 1.98, Dominant Max HLOD = 1.25, Recessive Max HLOD = 0.67 in BPI-restricted pedigrees	the absolute value of the resulting scores remained moderate the absolute value of the resulting scores remained moderate	Negative