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	Kremeyer, B., 2006 PMID: 16741941
Citation	Kremeyer, B., I. Herzberg, et al. (2006). "Transmission distortion of BDNF variants to bipolar disorder type I patients from a South American population isolate." Am J Med Genet B Neuropsychiatr Genet 141B(5): 435-439.
Disease Type	Bipolar I Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	224 bipolar type I patients and available parents (comprising a total of 212 nuclear families)
SNP/Region/Marker Size	2 variants
Predominant Ethnicity
Population	South American
Gender	84 males, 140 females

Detail Info

Sample Diagnosis	Diagnostic Interview for Genetic Studies (DIGS)
Sample Status	Of 224 BP I patients, with a mean age of onset 24.1 (SD=8.2) years, 176 have no known recent common ancestors and where included in the study as trios (both parents available for study) or duos (only one parent available). The remaining 48 cases are members of 6 extended pedigrees with a range of affected individuals between 4 and 11. Patients were recruited in the city of Medellin (Antioquia, Colombia), at Hospital Mental de Antioquia, Hospital San Vicente de Paul and Clinica Samein. Inclusion criteria required that cases had at least 6/8 great-grand parents born in Antioquia and at least two hospitalizations, the first one occurring by the age of 45.
Technique	genotyping
Statistical Method	Haplotype frequencies and two-locus linkage disequilibrium (LD) were estimated using the TDTPHASE v2.4 program. The Transmission Disequilibrium Test was applied as implemented in the TRANSMIT program, version 2.5.4. The method used by TRANSMIT is based on an extension of the test of Spielman et al., allowing the analysis of data from patients with only one available parent and applicable to multilocus data (even under uncertain phase). The statistic estimated by TRANSMIT follows a Chi square distribution and is calculated as (O-E)²/Var(O-E) where O and E refer to the number of observed and expected transmissions of alleles/haplotypes.
Result Summary	Significant excess transmission of the rs6265 G allele to cases was observed (chi(2)=10.77, d.f.=1, P=0.001). Two-locus haplotype analysis showed a significant global transmission distortion (chi(2)=16.059, d.f.=7, P=0.025) with an excess transmission of a haplotype comprising the rs6265 G allele and microsatellite allele 227. These results are consistent with previous studies pointing to a role for BDNF in susceptibility to mood disorders.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs6265	BDNF BDNF-AS	A/G		P-value = 0.001, X²=10.77, df=1	At the Val66Met polymorphism there is a significant over-tra...... At the Val66Met polymorphism there is a significant over-transmission of the Val allele. More...	Positive

Haplotypes reported by this study for BD (count: 15)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs6265 - BDNF_(CA)	Met-223	BDNF	P-value = 0.236, X<sup>2</sup>=1.41, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Met-221	BDNF	P-value = 0.811, X<sup>2</sup>=0.06, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Val-231	BDNF	P-value = 0.533, X<sup>2</sup>=0.39, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Val-229	BDNF	P-value = 0.748, X<sup>2</sup>=0.1, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Val-227	BDNF	P-value = 0.006, X<sup>2</sup>=7.67, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The two-locus haplotype analyses indicate nominally signific...... The two-locus haplotype analyses indicate nominally significant over-transmission of the Val-227 haplotype. The global two locus test indicates significant transmission distortion. More...	Positive
rs6265 - BDNF_(CA)	Val-225	BDNF	P-value = 0.953, X<sup>2</sup>=0, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Val-233	BDNF	P-value = 0.274, X<sup>2</sup>=1.2, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Met-231	BDNF	P-value = 0.02, X<sup>2</sup>=5.4, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The two-locus haplotype analyses indicate non-significant un...... The two-locus haplotype analyses indicate non-significant under-transmission of the two haplotypes carrying the Met allele (Met-227 and Met-231). The global two locus test indicates significant transmission distortion. More...	Positive
rs6265 - BDNF_(CA)	Met-229	BDNF	P-value = 0.68, X<sup>2</sup>=0.17, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Met-227	BDNF	P-value = 0.018, X<sup>2</sup>=5.59, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The two-locus haplotype analyses indicate non-significant un...... The two-locus haplotype analyses indicate non-significant under-transmission of the two haplotypes carrying the Met allele (Met-227 and Met-231). The global two locus test indicates significant transmission distortion. More...	Positive
rs6265 - BDNF_(CA)	Met-225	BDNF	P-value = 0.844, X<sup>2</sup>=0.04, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Val-223	BDNF	P-value = 0.207, X<sup>2</sup>=1.59, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Val-221	BDNF	P-value = 0.327, X<sup>2</sup>=0.96, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Val-219	BDNF	P-value = 0.764, X<sup>2</sup>=0.09, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative
rs6265 - BDNF_(CA)	Met-233	BDNF	P-value = 0.699, X<sup>2</sup>=0.15, df=1; global P-value = 0.025, X<sup>2</sup>=16.059, df=7	The global two locus test indicates significant transmission...... The global two locus test indicates significant transmission distortion. More...	Negative

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
BDNF (CA)	BDNF	microsatellite			P-value = 0.767, X²=0.09, df=1 for 219; P-value = 0.386, X²=0.75, df=1 for 221; P-value = 0.128, X²=2.32, df=1 for 223; P-value = 0.853, X²=0.03, df=1 for 225; P-value = 0.099, X²=2.72, df=1 for 227; P-value = 0.925, X²=0.01, df=1 for 229; P-value = 0.06, X²=3.55, df=1 for 231; P-value = 0.498, X²=0.46, df=1 for 233; Global P-value = 0.298, X²=7.26, df=6	For BDNF(CA), there is excess transmission of allele 227 and...... For BDNF(CA), there is excess transmission of allele 227 and under-transmission of allele 231, which do not reach nominal statistical significance. A global test of transmission disequilibrium at BDNF(CA) is not significant. More...	Negative

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