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	Kakiuchi, C.,2003 PMID: 12949534
Citation	Kakiuchi, C., K. Iwamoto, et al. (2003). "Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder." Nat Genet 35(2): 171-175.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	For case-control study:197 unrelated individuals with bipolar disorder (140 with bipolar I disorder (BPI) and 57 with bipolar II disorder (BPII)),and 451 unrelated control subjects.For transmission disequilibrium test,88 trio samples.
SNP/Region/Marker Size	1 variant
Predominant Ethnicity
Population	Japanese and NIMH collections

Detail Info

Sample Diagnosis	DSM
Sample Status	The subjects for the association study of XBP1 were 197 unrelated individuals with bipolar disorder (140 with bipolar I disorder (BPI) and 57 with bipolar II disorder (BPII)), who were tracked through at the hospitals or clinics participating in this study, and 451 unrelated control subjects who were recruited from the staffs and students of participating institutes. We made diagnosis of bipolar disorder using the DSM-IV criteria (American Psychiatric Association, 1994). For transmission disequilibrium test, we obtained 88 trio samples (77 trios with a proband with BPI and 11 trios with a proband with BPII) from National Institute of Mental Health (NIMH) genetics initiative pedigrees.
Technique	genotyping
Statistical Method	the Chi-square test ,Transmission disequilibrium test
Result Summary	A polymorphism (-116C-->G) in the promoter region of XBP1, affecting the putative binding site of XBP1, was significantly more common in Japanese patients (odds ratio = 4.6) and overtransmitted to affected offspring in trio samples of the NIMH Bipolar Disorder Genetics Initiative. XBP1-dependent transcription activity of the -116G allele was lower than that of the -116C allele, and in the cells with the G allele, induction of XBP1 expression after ER stress was markedly reduced. Valproate, one of three mood stabilizers, rescued the impaired response by inducing ATF6, the gene upstream of XBP1. These results indicate that the -116C-->G polymorphism in XBP1 causes an impairment of its positive feedback system and increases the risk of bipolar disorder.

Other variants reported by this study for BD (count: 1)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
XBP1 -116C>G	XBP1	point mutation	C>G		Association analysis:case-control study, genotype P-value = 0.00026(BPD), 0.0040(BP-I), 0.023(BP-II);allele P-value = 0.010(BPD), 0.081(BP-I), 0.015(BP-II);TDT for G allele, P-value = 0.047(BPD), 0.027(BP-I)	Significant associations were found in BPD patients. Significant associations were found in BPD patients.	Positive

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