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	Muller, D. J., 2006 PMID: 17012654
Citation	Muller, D. J., V. de Luca, et al. (2006). "Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder: family-based association study." Br J Psychiatry 189: 317-323.
Disease Type	Bipolar Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	312 nuclear families with at least one offspring, including 1043 people, 350 with bipolar disorder and 693 non-affected relatives.
SNP/Region/Marker Size	6 variants
Predominant Ethnicity	Caucasian
Population	Canadian
Gender	131 males and 219 females
Age Group	adults : Participants' mean age was 35.4 years (s.d.=10.3).

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	The total sample comprised 1043 people, 350 with bipolar disorder (131 males and 219 females) and 693 non-affected relatives. The distribution of bipolar disorder I and II according to DSM-IV criteria was assigned as follows: I, 200; I with rapid cycling, 27; I with seasonal patterns, 4; I with mixed episodes, 3; II, 57; II with rapid cycling, 31; II with seasonal patterns, 8. One person had a diagnosis of bipolar disorder not otherwise specified and 19 schizoaffective disorder, bipolar type. DSM-IV defines rapid cycling as the occurrence of four or more (depressive and/or manic) mood episodes within 12 months. The mean age at onset is 20.1 years (s.d.=7.5).
Technique	genotyping
Statistical Method	Association tests and haplotype analyses between BDNF markers and bipolar disorder were performed using TDTPHASE. Linkage disequilibrium and identification of haplotype blocks within the BDNF gene were performed using HAPLOVIEW. The standard Lewontin D' and correlation coefficient r2 were calculated using the expectation maximisation algorithm implemented in HAPLOVIEW.
Result Summary	The SNPs hCV11592756 and rs2049045, the Val66Met and GT(n) were significantly associated with bipolar disorder using transmission disequilibrium analyses (P=0.02, 0.009, 0.001 and 0.008 respectively). The effect at these markers was mainly driven by the rapid-cycling patients. Within bipolar disorder, variation in the BDNF gene appears to predict risk for developing rapid cycling according to DSM-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 BDNF and bipolar disorder.

SNPs reported by this study for BD (count: 3)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs2049045	BDNF BDNF-AS	G/C		TDTPHASE P-value = 0.009, df=1, LRS=6.67	Significant association between the total sample and the BDN...... Significant association between the total sample and the BDNF gene was found for rs2049045. Over-transmission was observed for the G allele of rs2049045. More...	Positive
rs3763965	LIN7C BDNF-AS BDNF	A/T		TDTPHASE P-value = 0.33, df=1, LRS=0.92	rs3763965 did not show an association with bipolar disorder. rs3763965 did not show an association with bipolar disorder.	Negative
rs2140887	KIF18A BDNF	A/G		TDTPHASE P-value = 0.94, df=1, LRS=0.004	rs2140887 did not show an association with bipolar disorder. rs2140887 did not show an association with bipolar disorder.	Negative

Haplotypes reported by this study for BD (count: 6)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
BDNF_hCV11592756 - BDNF_Val66Met	A-G	BDNF	TDTPHASE P-value = 0.0008, X<sup>2</sup>=11.09, RR=1.54	The strongest results were obtained when the Val allele was ...... The strongest results were obtained when the Val allele was combined with either marker hCV11592756 or allele 3 of the GT(n) repeat polymorphism. More...	Positive
BDNF_hCV11592756 - BDNF_Val66Met - BDNF_GT(n)	A-G-3	BDNF	TDTPHASE P-value = 0.008, X<sup>2</sup>=7.04, RR=0.37		Positive
BDNF_hCV11592756 - rs2049045	A-G	BDNF	TDTPHASE P-value = 0.01, X<sup>2</sup>=6.46, RR=1.41		Positive
BDNF_Val66Met - BDNF_GT(n)	G-3	BDNF	TDTPHASE P-value = 0.0008, X<sup>2</sup>=11.2, RR=2.29	The strongest results were obtained when the Val allele was ...... The strongest results were obtained when the Val allele was combined with either marker hCV11592756 or allele 3 of the GT(n) repeat polymorphism. More...	Positive
BDNF_hCV11592756 - BDNF_Val66Met - BDNF_GT(n) - rs2049045	A-G-3-G	BDNF	TDTPHASE P-value = 0.008, X<sup>2</sup>=6.37, RR=0.36	The A-Val-3-G haplotype proved to be significantly overtrans...... The A-Val-3-G haplotype proved to be significantly overtransmitted (49:25) in participants with bipolar disorder. More...	Positive
BDNF_hCV11592756 - BDNF_Val66Met - rs2049045	A-G-G	BDNF	TDTPHASE P-value = 0.001, X<sup>2</sup>=10.43, RR=2.13		Positive

Other variants reported by this study for BD (count: 3)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
BDNF Val66Met	BDNF	point mutation	A/G		TDTPHASE P-value = 0.001, df=1, LRS=10.62; P-value = 0.01 for bipolar disorder I, P-value = 0.02 for bipolar disorder II	Significant association between the total sample and the BDN...... Significant association between the total sample and the BDNF gene was found for Val66Met. Over-transmission was observed for the Val (or G) allele of Val66Met. When participants with bipolar disorder were divided into two groups (bipolar disorder I and II), a significant association was found for the Val66Met polymorphism of the BDNF gene. More...	Positive
BDNF hCV11592756	BDNF	point mutation	G/A		TDTPHASE P-value = 0.02, df=1, LRS=5.4	Significant association between the total sample and the BDN...... Significant association between the total sample and the BDNF gene was found for hCV11592756. Over-transmission was observed for the A allele of hCV11592756. More...	Positive
BDNF (GT)n	BDNF	microsatellite			TDTPHASE P-value = 0.17, df=8, LRS=11.66; TDTPHASE P-value = 0.008, df=1, LRS=6.87 for allele 3 vs other alleles	Significant association between the total sample and the BDN...... Significant association between the total sample and the BDNF gene was found for GT(n) repeat polymorphism. Over-transmissions was observed for allele 3 of the GT(n) repeat. More...	Positive

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