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	Kealey, C.,2005 PMID: 15909293
Citation	Kealey, C., S. Roche, et al. (2005). Linkage and candidate gene analysis of 14q22-24 in bipolar disorder: support for GCHI as a novel susceptibility gene. Am J Med Genet B Neuropsychiatr Genet 136B(1): 75-80.
Disease Type	Bipolar Disorder
Study Design	family-based
Study Type	Candidate-region linkage study and candidate-gene association study
Sample Size	49 sib-pair families for linkage study and 93 BPI probands and their parents for association study
SNP/Region/Marker Size	13 microsatellite markers and 4 SNPs
Predominant Ethnicity	Caucasian
Population	Irish

Detail Info

Sample Diagnosis	DSM
Sample Status	Forty-nine families, all of Irish origin, were collected as part of a systematic screen of bipolar mood disorder clinics from throughout Ireland by a single clinical team (The Depression Research Unit, St. Patrick's Hospital, Dublin, Ireland). To be included in the National Sib-Pair Collection, each family must have a BPI proband plus at least one other sib-pair with a diagnosis of affected under a broad definition (BPI, BPII,schizoaffective [SA] disorder, and recurring unipolar [RUP]depression). Trained psychiatric nurses interviewed all family members using the Schedule for Affective Disorders and Schizophrenia (Lifetime Version; SADS-LB). Information from previous hospitalizations and clinical records was also collated.Diagnoses were reviewed by a consultant psychiatrist and all met DSM-IV criteria (Diagnostic and Statistical Manual,American Psychiatric Association, 1994). BPI probands and their parents (trios) were ascertained in a similar manner to the sib-pair collection. Control individuals were obtained from the Blood Transfusion Service Board (Dublin and Cork) and the Northern Ireland Blood Transfusion Service (Belfast).Controls were not screened for psychiatric illness, although, a prerequisite for blood donation was that individuals could not be on long-term medication.
Technique	RFLP and genotyping
Statistical Method	Linkage Analysis:Allele frequencies were estimated using FBAT software [Horvath et al., 2001].Two-point and multipoint non-parametric lod (NPL) scores and their corresponding P-values were obtained using Genehunther(version 2.1) [Kruglyak et al., 1996].Association Analysis:All genotypic data was analyzed manually using the transmission disequilibrium test (TDT).
Result Summary	Effectively, P-values <0.05 were observed for a region extending over 41.88 cM, with the marker D14S281 displaying a peak multipoint non-parametric lod (NPL) score of 2.72 and an associated P-value of 0.003. Support for this finding was also obtained from flanking markers indicating excess allele sharing at 14q22-24 in Irish bipolar sib-pairs. A web-based candidate gene search of 14q22-24 resulted in the selection of GTP cyclohydrolase I (GCHI), located 200 kb 3' of D14S281, as the best plausible candidate gene for involvement in BPD. An association study between BPD and a novel single nucleotide polymorphism (SNP) in GCHI (G to A at position -959 bp, upstream of the ATG codon), is also presented here. This study revealed that the variant A allele is preferentially transmitted to BPI probands (chi(2) = 4.54, P = 0.033) suggesting that variants within GCHI may contribute to BPD in the Irish population.

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
GCH1 -959G/A	GCH1	point mutation	G/A		Allelic association:TDT:X²=4.54, P-value = 0.033	The alleles at the polymorphism were significantly associate...... The alleles at the polymorphism were significantly associated with the BPI. More...	Positive

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

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