Genetic variation of brain-derived neurotrophic factor (BDNF) in bipolar disorder: case-control study of over 3000 individuals from the UK.
BACKGROUND
Brain-derived neurotrophic factor (BDNF) influences neuronal survival, proliferation and plasticity. Three family-based studies have shown association of the common Valine (Val) allele of the Val66Met polymorphism of the BDNF gene with susceptibility to bipolar disorder.


OBJECTIVE
To replicate this finding.


METHODS
We genotyped the Val66Met polymorphism in our UK White bipolar case-control sample (n=3062).


RESULTS
We found no overall evidence of allele or genotype association. However, we found association with disease status in the subset of 131 individuals that had experienced rapid cycling at some time (P=0.004). We found a similar association on re-analysis of our previously reported family-based association sample (P < 0.03, one-tailed test).


CONCLUSIONS
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.
Green
Elaine K
EK
Department of Psychological Medicine, Henry Wellcome Building, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF4 4XN, Wales, UK.
Raybould
Rachel
R
Macgregor
Stuart
S
Hyde
Sally
S
Young
Allan H
AH
O'Donovan
Michael C
MC
Owen
Michael J
MJ
Kirov
George
G
Jones
Lisa
L
Jones
Ian
I
Craddock
Nick
N
D001714:Bipolar Disorder / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D004739:England; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D014633:Valine / Q000235:genetics*; D014852:Wales
D019208:Brain-Derived Neurotrophic Factor; D014633:Valine