Association study of candidate variants from brain-derived neurotrophic factor and dystrobrevin-binding protein 1 with neuroticism, anxiety, and depression.
OBJECTIVE
Association of the valine/methionine variant at codon 66 (Val66Met) of brain derived neurotrophic factor (BDNF) has been reported inconsistently across a spectrum of psychiatric disorders. Haplotypes of six tagging single nucleotide polymorphisms (SNPs) of a 37-kb region of dystrobrevin-binding protein 1 (DTNBP1) were found to be associated with schizophrenia. These haplotypes have not been studied extensively for other psychiatric disorders but are plausible candidates for anxiety and depression disorders. Here, association between variants of BDNF and DTNBP1, and multiple anxiety and depression phenotypes is explored.


METHODS
Study participants were selected as sibling pairs that were either concordant or discordant for extreme neuroticism scores from a total sample of 18 742 Australian twin individuals and their siblings. All participants completed detailed Composite International Diagnostic Interview from which diagnoses of Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV depression and anxiety disorders were determined. Six hundred and seventy-four participants had a diagnosis of anxiety and/or depression from 492 families. The BDNF Val66Met and six DTNBP1 (rs3213207, rs1011313, rs2619528, rs760761, rs1018381, rs2619538) SNPs were genotyped on samples from study participants (n=2045 from 987 families) and, where possible, their parents (n=787). Family-based association tests were conducted between the individual SNPs and the DTNBP1 six SNP haplotypes and anxiety, depression, and neuroticism.


RESULTS
We found no convincing evidence for association between any of the variants studied and anxiety, depression, or neuroticism.


CONCLUSIONS
This study sample is relatively large but our results do not support an association between BDNF Val66Met and anxiety, depression, or neuroticisim. DTNBP1 haplotypes, which have been found to be risk factors for schizophrenia, are unlikely to be risk factors for anxiety and depression.
Wray
Naomi R
NR
Queensland Institute of Medical Research, Brisbane, Australia. Naomi.Wray@qimr.edu.au
James
Michael R
MR
Handoko
Herlina Y
HY
Dumenil
Troy
T
Lind
Penelope A
PA
Montgomery
Grant W
GW
Martin
Nicholas G
NG
D000328:Adult; D001007:Anxiety / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D049029:Dystrophin-Associated Proteins / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D015810:Linkage Disequilibrium; D009479:Neuropeptides / Q000235:genetics*; D009497:Neurotic Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D019208:Brain-Derived Neurotrophic Factor; C490915:DTNA protein, human; D049029:Dystrophin-Associated Proteins; D009479:Neuropeptides