Gene Report

Basic Info
Approved Symbol BDNF
Approved Name brain-derived neurotrophic factor
Name Alias neurotrophin
Location 11p14.1
Position chr11:27654893-27722058, -1
External Links HGNC: 1033
Entrez Gene: 627
Ensembl: ENSG00000176697
UCSC: uc009yje.3
No. of Studies 37 (Positive: 24; Negative: 12; trend: 1)
Overlap with SZ? YES
Overlap with MDD? YES
Gene related studies (count: 37)
Reference Tested Markers Statistical Values/Author Comments Result Category Comment on Study
Hong, C. J.,2003 Other variant: BDNF_Val66Met Given the fact that the positive association between BDNF gene Val66Met polymorphism and bipolar disorder has only been demonstrated for a Caucasian population but not for a Japanese analog or our Chinese sample, it appears likely that this association is ethnicity dependent. Negative Comment on Study
Nakata, K.,2003(a) Other variant: BDNF_-1360C>T, BDNF_196G/A The results suggest that the BDNF gene is unlikely to confer susceptibility to BPD. Positive Comment on Study
Sklar, P.,2002 Other variant: BDNF_12910C/A, BDNF_-1480C/G, BDNF_3071G/A, BDNF_9202G/A, BDNF_11757C/G, BDNF_14569G/A, BDNF_196G/A, BDNF_-633T/A, BDNF_Val66Met This study of 76 candidate genes has identified BDNF as a potential risk allele that will require additional study to confirm. Positive Comment on Study
Neves-Pereira, M.,2002 Haplotype: [BNDF_(GT)n] - (BNDF_val66met)(allele 10-A), [BNDF_(GT)n] - (BNDF_val66met)(allele 1-A), [BNDF_(GT)n] - (BNDF_val66met)(allele 1-G), [BNDF_(GT)n] - (BNDF_val66met)(allele 2-A), [BNDF_(GT)n] - (BNDF_val66met)(allele 2-G), [BNDF_(GT)n] - (BNDF_val66met)(allele 3-A), [BNDF_(GT)n] - (BNDF_val66met)(allele 3-G), [BNDF_(GT)n] - (BNDF_val66met)(allele 4-A), [BNDF_(GT)n] - (BNDF_val66met)(allele 4-G), [BNDF_(GT)n] - (BNDF_val66met)(allele 5-G), [BNDF_(GT)n] - (BNDF_val66met)(allele 7-G)
Other variant: BDNF_(GT)n, BDNF_Val66Met
Our results suggested that a DNA variant in the vicinity of the BDNF locus confers susceptibility to BP. Positive Comment on Study
Kunugi, H.,2004 Other variant: BDNF_Val66Met The Val66Met polymorphism of the BDNF gene is unrelated to the development or clinical features of bipolar disorder, at least in a Japanese population. Negative Comment on Study
Geller, B.,2004 Other variant: BDNF_Val66Met This finding in child bipolar disorder is consistent with data for adults with bipolar disorder that show preferential transmission of the Val66 allele. Positive Comment on Study
Wang, Z.,2012 SNP: rs6265 Although these results should be interpreted with caution because of the limited sample for Val/Val genotype in BPD-II patients (N = 5), these findings strengthen the hypothesis that BDNF pathway gets involved in the etiology and pharmacology of BPD and suggest the differences between BPD-I and BPD-II. Positive Comment on Study
Hamshere, M. L.,2012 Other variant: BDNF_Val66Met The significant interaction effect for the Val/Val genotype of the BDNF Val66Met polymorphism and A1/A2 genotype of DRD2/ANKK1 Taq1A polymorphism was found only in BP-II patients. We provide initial evidence that the BDNF Val66Me and DRD2/ANKK1 Taq1A polymorphisms interact only in BP-II disorder and that BP-I and BP-II are genetically distinct. Positive Comment on Study
Schumacher, J.,2005 SNP: rs6265, rs988748
Haplotype: rs988748 - BDNF_(GT)n - rs6265(C-166bp-G), rs988748 - BDNF_(GT)n - rs6265(C-168bp-G), rs988748 - BDNF_(GT)n - rs6265(C-170bp-G), rs988748 - BDNF_(GT)n - rs6265(C-172bp-G), rs988748 - BDNF_(GT)n - rs6265(C-174bp-G), rs988748 - BDNF_(GT)n - rs6265(G-170bp-A), rs988748 - BDNF_(GT)n - rs6265(G-174bp-A), rs988748 - BDNF_(GT)n - rs6265(G-174bp-G), rs988748 - BDNF_(GT)n - rs6265(G-176bp-A)
Other variant: BDNF_(GT)n
Our study does not lend much support to a role for BDNF in the etiopathogenesis of BPAD but at the same time cannot unequivocally rule it out. Trend Comment on Study
Neves-Pereira, M.,2005 SNP: rs6265
Haplotype: rs6265 - microsatellite (GT)n(A-(GT1)), rs6265 - microsatellite (GT)n(G-(GT1))
Haplotype analysis of val/met SNP and a dinucleotide repeat polymorphism in the putative promoter region revealed highly significant (P<E-08) under-representation of the methionine or met-1 haplotype in the schizophrenic but not the BP population. Negative Comment on Study
Matsuo, K.,2009 Other variant: BDNF_Val66Met The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD. Positive Comment on Study
Chepenik, L. G.,2009 Other variant: BDNF_Val66Met In sum, this study of the val66met polymorphism provides preliminary evidence that variation in BNDF has the potential to influence hippocampus structure in BD, and carriers of the met allele may be a subgroup within BD more vulnerable to hippocampus-related deficits. Positive Comment on Study
Sears, C.,2011 SNP: rs10835210, rs11030104, rs11030107, rs11030119, rs12273363, rs1519480, rs6265, rs7103873 Our results support the hypothesis that some BDNF gene polymorphisms may be contributing factors in the pathogenesis of BD. Positive Comment on Study
Neves, F. S.,2011 SNP: rs2049045, rs4923463, rs6265, rs7103411 No genotypic, allelic or haplotype differences were found between bipolar patients and healthy controls. Negative Comment on Study
Hosang, G. M.,2010 SNP: rs6265 The Met containing genotype of BNDF gene was significantly associated with BD. Positive Comment on Study
Soronen, P.,2011 SNP: rs11030102 No significant association of this gene was observed in BD. Negative Comment on Study
Okada, T., 2006 Haplotype: BDNF_LCPR - BDNF_Val66Met(A1-Val ), BDNF_LCPR - BDNF_Val66Met(A2-Val ), BDNF_LCPR - BDNF_Val66Met(A3-Val ), BDNF_LCPR - BDNF_Val66Met(A4-Val ), BDNF_LCPR - BDNF_Val66Met(A4-Met ), BDNF_LCPR - BDNF_Val66Met(A5-Val ), BDNF_LCPR - BDNF_Val66Met(A5-Met )
Other variant: BDNF-LCPR
Our results suggest that the BDNF-LCPR is a functional variation that confers susceptibility to bipolar disorder and affects transcriptional activity of the BDNF gene. Positive Comment on Study
Skibinska, M., 2004 Other variant: BDNF_Val66Met No association was found between the studied polymorphism and schizophrenia or bipolar affective disorder either for genotype or allele distribution. Negative Comment on Study
Huang, C. C.,2012 Other variant: BDNF_Val66Met BDNF Val/Va: logistic Regression P-value=0.82, OR=1.10, 95% CI=0.47-2.60 in BPI, P-value=0.04, OR=0.40, 95% CI=0.16-0.97 in BPII, BDNF Val/Met: logistic Regression P-value=0.33, OR=1.18, 95% CI=0.54-2.58 in BPI, P-value=0.36, OR=1.39, 95% CI=0.69-2.80 in BPII. Multiple logistic regression analysis, controlled for age and gender, showed a significant main effect of the Val/Val genotype on the BDNF Val66Met gene in the BP-II group. Positive Comment on Study
Liu, L., 2008 SNP: rs11030104, rs12273363, rs1519480, rs2030324, rs2883187, rs6265, rs7103411, rs7127507, rs7934165, rs988748 Evidence of association (p<0.05) was found with several of the SNPs using multiple models of bipolar disorder; one of these SNPs also showed evidence of association (p<0.05) with rapid cycling.. These results provide further evidence that variation in BDNF affects the risk for bipolar disorder. Positive Comment on Study
Tang, J., 2008 Other variant: BDNF_C270T, BDNF_Val66Met The study demonstrates that the BDNF C-270T and Val66Met polymorphisms are unlikely to contribute to the genetic predisposition to BPD as a whole. But Val66Met may be associated with susceptibility to the early age of onset subset of the disorder. Negative Comment on Study
Vincze, I., N., 2008 Haplotype: BDNF-LCPR - A-633T - G196A(STG ), BDNF-LCPR - A-633T - G196A(SAG ), BDNF-LCPR - A-633T - G196A(LAA ), BDNF-LCPR - A-633T - G196A(LAG ), BDNF-LCPR - A-633T - G196A(SAA ), BDNF-LCPR - A-633T - G196A(STA ), BDNF-LCPR - A-633T - G196A(LTG )
Other variant: BDNF_196G/A, BDNF_A-633T, BDNF-LCPR
BDNF G196A (Val66Met) genotypic P-value = 0.0071; Allelic P-value = 0.12. We replicated the association previously reported between BDNF G196A (Val66Met) polymorphism and BD Positive Comment on Study
Oswald, P., 2004 SNP: rs6265
Haplotype: g.196A_ g.11757G()
Other variant: BDNF_g.11757C>G
We failed to replicate previous findings implicating BDNF in the aetiology of BPAD Negative Comment on Study
Chang, Y. H.,2013 Other variant: BDNF_Val66Met The involvement of the dopaminergic pathway in AD was confirmed, particularly with BP-II rather than BP-I. Because the Val/Val genotype of the BDNF Val66Met polymorphism, rather than the other two polymorphisms, has been associated with anxiety, it seems to affect BP-I comorbid with AD without the involvement of the DRD3 Seg9Gly polymorphism, but may modify the involvement of DRD3 Gly/Gly in BP-II comorbid with AD. Positive Comment on Study
Lee, S. Y.,2012(a) Other variant: BDNF_Val66Met We provide initial evidence that the BDNF Val66Met and DRD3 Ser9Gly genotypes interact only in bipolar-II disorder and that bipolar-I and bipolar-II may be genetically distinct. Positive Comment on Study
Lee, S. Y.,2012(b) Other variant: BDNF_Val66Met Our findings provide initial evidence that the COMT and BDNF genes interact in bipolar-II without AD. Our findings suggest the involvement of dopaminergic pathway in the pathogenesis of bipolar-II. Positive Comment on Study
Ivanova, M. A.,2012 SNP: rs6265, rs16917237, rs12273363
Haplotype: rs6265 - rs16917237(C-G), rs16917237 - rs12273363(G-T), rs6265 - rs16917237 - rs12273363(C-G-T), rs16917237 - rs12273363(T-T)
In summary, the current study lends support to the role of BDNF as a predisposing or a modifying factor in the etiology of AD. Positive Comment on Study
Kanazawa, T., 2007 SNP: rs6265 The results indicate there is a lack of association between the Val66Met polymorphism of BDNF and either schizophrenia or bipolar disorder. Negative Comment on Study
Gonzalez-Castro, T. B., 2014 SNP: rs6265 No significant associations were observed in all models and subgroups. Negative Comment on Study
Tramontina, J., 2007 Other variant: BDNF_Val66Met No significant differences were found in the frequency of the BDNF val66met genotype or allele distribution between patients and controls. Negative Comment on Study
Green, E. K., 2006 Other variant: BDNF_Val66Met Variation at the Val66Met polymorphism of BDNF does not play a major role in influencing susceptibility to bipolar disorder as a whole, but is associated with susceptibility to the rapid cycling subset of the disorder. Positive Comment on Study
Kremeyer, B., 2006 SNP: rs6265
Haplotype: rs6265 - BDNF_(CA)(Met-221), rs6265 - BDNF_(CA)(Met-223), rs6265 - BDNF_(CA)(Met-225), rs6265 - BDNF_(CA)(Met-227), rs6265 - BDNF_(CA)(Met-229), rs6265 - BDNF_(CA)(Met-231), rs6265 - BDNF_(CA)(Met-233), rs6265 - BDNF_(CA)(Val-219), rs6265 - BDNF_(CA)(Val-221), rs6265 - BDNF_(CA)(Val-223), rs6265 - BDNF_(CA)(Val-225), rs6265 - BDNF_(CA)(Val-227), rs6265 - BDNF_(CA)(Val-229), rs6265 - BDNF_(CA)(Val-231), rs6265 - BDNF_(CA)(Val-233)
Other variant: BDNF_(CA)
These results are consistent with previous studies pointing to a role for BDNF in susceptibility to mood disorders. Positive Comment on Study
Muller, D. J., 2006 SNP: rs2049045, rs2140887, rs3763965
Haplotype: BDNF_hCV11592756 - BDNF_Val66Met(A-G), BDNF_hCV11592756 - BDNF_Val66Met - BDNF_GT(n)(A-G-3), BDNF_hCV11592756 - BDNF_Val66Met - BDNF_GT(n) - rs2049045(A-G-3-G), BDNF_hCV11592756 - BDNF_Val66Met - rs2049045(A-G-G), BDNF_hCV11592756 - rs2049045(A-G), BDNF_Val66Met - BDNF_GT(n)(G-3)
Other variant: BDNF_(GT)n, BDNF_hCV11592756, BDNF_Val66Met
Within bipolar disorder, variation in the BDNF gene appears to predict risk for developing rapid cycling according toDSM-IV. Incorporating this clinical sub-phenotyping into other studies of the BDNF gene may help to resolve some of the inconsistencies reported thus far concerning BDNFand bipolar disorder. Positive Comment on Study
Lohoff, F. W.,2005(c) SNP: rs6265 Results confirm previous findings and suggest that the Val allele increases risk for BPI in patients of European descent. Positive Comment on Study
Yosifova, A.,2009 SNP: rs2049045, rs4923463, rs6265 Significant association of SNP in this gene with BD in our population was observed. Positive Comment on Study
Mick, E.,2009 Other variant: BDNF_Val66Met We failed to identify an association with the val66 allele in BDNF with pediatric bipolar disorder.. Negative Comment on Study
Xu, J., 2010 SNP: rs6265 We found that the BDNF genotype is associated with BPD in this population. Positive Comment on Study
Gene functional annotation
Gene related GO terms (count: 63)

GO terms by PBA (count: 2)

GO terms by database search (count: 61)

Gene related KEGG pathways (count: 2)

KEGG pathways by PBA (count: 1)

KEGG pathways by database search (count: 1)

Gene related BioCarta pathways (count: 0)

Gene related interactors from protein-protein interactions data in HPRD (count: 6)

Related other genetic factors
Gene related SNPs (count: 37)

Literature-origin SNPs (count: 20)

LD-proxies (count: 17)

Gene related CNVs (count: 0)

Gene related other variants (count: 17)

Gene related regions (count: 2)

Overlap with schizophrenia (SZ) and major depressive disorder (MDD)
Gene relationship with SZ

Overlap with SZ from cross-disorder studies (count: 4)

Overlap with SZ from candidate gene intersection analysis (count: 47)

Gene relationship with MDD

Overlap with MDD from cross-disorder studies (count: 3)

Overlap with MDD from candidate gene intersection analysis (count: 13)

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Region: chr11:27654893..27722058 View in gBrowse
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