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	Sklar, P.,2002 PMID: 12140781
Citation	Sklar, P., S. B. Gabriel, et al. (2002). "Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor." Mol Psychiatry 7(6): 579-593.
Disease Type	Bipolar Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	136 parent-proband trios
SNP/Region/Marker Size	90 SNPs
Predominant Ethnicity	Caucasian
Population	American,British and NIMH collections

Detail Info

Sample Diagnosis	DSM and RDC
Sample Status	Hopkins samples Pedigrees were ascertained from inpatient and outpatient clinics in Maryland and Iowa. Most of the families have been previously described. The ascertainment criteria were: a treated bipolar I proband, at least two affected firstdegree relatives and unilineal transmission.Probands had the following diagnoses: 106 BP1, 26 BP2 and four schizoaffective-manic (SA-M). All BP2 and SA-M probands had a BP1 sibling and both siblings were used in the analyses. Diagnoses were established using the Research Diagnostic Criteria (RDC). NIMH sample DNA was obtained from the NIMH Genetics Initiative. Pedigree ascertainment and diagnoses were as described.Probands had the following diagnoses: 149 BP1, one BP2 and five SA-M. Diagnoses of BP1 and SA-M were established using DSM-III-R criteria and BP2 by the Research Diagnostic Criteria (RDC). UK sample Pedigrees were ascertained as described from clinics in Britain. All probands were diagnosed with BP1 and the diagnoses were established using DSM-IV criteria. Non-BP sample The sample is comprised of 333 Scandanavian parent-proband trios where the proband has either type 2 diabetes, impaired glucose tolerance,or impaired fasting glucose as described.These patients were not screened for the presence or absence of bipolar disorder.
Replication Size	334 parent-proband trios
Technique	genotyping
Statistical Method	the transmission disequilibrium test (TDT)
Result Summary	Strong LD was observed across this region and all adjacent pairwise haplotypes showed excess transmission to the bipolar proband. Analysis of these haplotypes using TRANSMIT revealed a global P value of 0.03. A single haplotype was identified that is shared by both the original dataset and the replication sample that is uniquely marked by both the rare A allele of the original SNP and a novel allele 11.5 kb 3'. Therefore, this study of 76 candidate genes has identified BDNF as a potential risk allele that will require additional study to confirm.

Other variants reported by this study for BD (count: 9)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
BDNF 11757C/G	BDNF	point mutation	C/G	C	Association analysis:TDT, Hopkins sample, T/NT=59/30, chi square=9.45, P-value = 0.0021;NIMH sample, T/NT=70/56, chi square=1.56, P-value = 0.106	Significant associations were found in Hopkins sample. Significant associations were found in Hopkins sample.	Positive
BDNF 14569G/A	BDNF	point mutation	G/A	G	Association analysis:TDT, Hopkins sample, T/NT=67/41, chi square=6.26, P-value = 0.0124;NIMH sample, T/NT=73/89, chi square=1.58, P-value = 0.209	Significant associations were found in Hopkins sample. Significant associations were found in Hopkins sample.	Positive
BDNF 196G/A	BDNF	point mutation	G/A	G	Association analysis:TDT, Hopkins sample, T/NT=53/34, chi square=4.1, P-value = 0.0416;NIMH sample, T/NT=70/55, chi square=1.8, P-value = 0.09;UK sample, T/NT=38/32, chi square=0.51, P-value = 0.24	Significant associations were found in Hopkins sample. Significant associations were found in Hopkins sample.	Positive
BDNF -633T/A	BDNF	point mutation	T/A	T	Association analysis:TDT, Hopkins sample, T/NT=38/67, chi square=8, P-value = 0.0047;NIMH sample, T/NT=89/83, chi square=0.21, P-value = 0.647;UK sample, T/NT=65/62, chi square=0.07, P-value = 0.79	Significant associations were found in Hopkins sample. Significant associations were found in Hopkins sample.	Positive
BDNF Val66Met	BDNF	point mutation	Val66Met		Association analysis:TDT, Hopkins sample, T/NT=53/34, chi square=4.1, P-value = 0.042, OR=1.56, OR(95%CI)=1.05-2.47;NIMH sample, T/NT=70/55, chi square=1.8, P-value = 0.09, OR=1.27, OR(95%CI)=0.92-1.84;UK sample, T/NT=38/32, chi square=0.51, P-value = 0.237, OR=1.19, OR(95%CI)=0.77-1.96;Replication samples(NIMH+UK), T/NT=108/87, chi square=2.26, P-value = 0.066, OR=1.24, OR(95%CI)=0.95-1.66	Significant associations were found in Hopkins sample. Significant associations were found in Hopkins sample.	Positive
BDNF 9202G/A	BDNF	point mutation	G/A	G	Association analysis:TDT, Hopkins sample, T/NT=58/40, chi square=3.31, P-value = 0.069;NIMH sample, T/NT=56/63, chi square=0.41, P-value = 0.521	No significant association was observed in BD. No significant association was observed in BD.	Negative
BDNF 3071G/A	BDNF	point mutation	G/A	G	Association analysis:TDT, Hopkins sample, T/NT=44/42, chi square=0.05, P-value = 0.8292;NIMH sample, T/NT=82/64, chi square=2.22, P-value = 0.136	No significant association was observed in BD. No significant association was observed in BD.	Negative
BDNF -1480C/G	BDNF	point mutation	C/G	C	Association analysis:TDT, Hopkins sample, T/NT=29/33, chi square=0.26, P-value = 0.6115;NIMH sample, T/NT=53/40, chi square=1.82, P-value = 0.178	No significant association was observed in BD. No significant association was observed in BD.	Negative
BDNF 12910C/A	BDNF	point mutation	C/A	C	Association analysis:TDT, Hopkins sample, T/NT=38/38, chi square=0, P-value = 1;NIMH sample, T/NT=51/67, chi square=2.17, P-value = 0.141	No significant association was observed in BD. No significant association was observed in BD.	Negative

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