PMID- 12140781
OWN - NLM
STAT- MEDLINE
DCOM- 20030211
LR  - 20061115
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 7
IP  - 6
DP  - 2002
TI  - Family-based association study of 76 candidate genes in bipolar disorder: BDNF is 
      a potential risk locus. Brain-derived neutrophic factor.
PG  - 579-93
AB  - Identification of the genetic bases for bipolar disorder remains a challenge for 
      the understanding of this disease. Association between 76 candidate genes and 
      bipolar disorder was tested by genotyping 90 single-nucleotide polymorphisms 
      (SNPs) in these genes in 136 parent-proband trios. In this preliminary analysis, 
      SNPs in two genes, brain-derived neurotrophic factor (BDNF) and the alpha subunit 
      of the voltage-dependent calcium channel were associated with bipolar disorder at 
      the P<0.05 level. In view of the large number of hypotheses tested, the two 
      nominally positive associations were then tested in independent populations of 
      bipolar patients and only BDNF remains a potential risk gene. In the replication 
      samples, excess transmission of the valine allele of amino acid 66 of BDNF was 
      observed in the direction of the original result in an additional sample of 334 
      parent-proband trios (T/U=108/87, P=0.066). Resequencing of 29 kb surrounding the 
      BDNF gene identified 44 additional SNPs. Genotyping eight common SNPs identified 
      three additional markers transmitted to bipolar probands at the P < 0.05 level. 
      Strong LD was observed across this region and all adjacent pairwise haplotypes 
      showed excess transmission to the bipolar proband. Analysis of these haplotypes 
      using TRANSMIT revealed a global P value of 0.03. A single haplotype was 
      identified that is shared by both the original dataset and the replication sample 
      that is uniquely marked by both the rare A allele of the original SNP and a novel 
      allele 11.5 kb 3'. Therefore, this study of 76 candidate genes has identified 
      BDNF as a potential risk allele that will require additional study to confirm.
FAU - Sklar, P
AU  - Sklar P
AD  - Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, 
      Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 
      sklar@genome.wi.mit.edu
FAU - Gabriel, S B
AU  - Gabriel SB
FAU - McInnis, M G
AU  - McInnis MG
FAU - Bennett, P
AU  - Bennett P
FAU - Lim, Y -M
AU  - Lim Y-
FAU - Tsan, G
AU  - Tsan G
FAU - Schaffner, S
AU  - Schaffner S
FAU - Kirov, G
AU  - Kirov G
FAU - Jones, I
AU  - Jones I
FAU - Owen, M
AU  - Owen M
FAU - Craddock, N
AU  - Craddock N
FAU - DePaulo, J R
AU  - DePaulo JR
FAU - Lander, E S
AU  - Lander ES
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
CIN - Mol Psychiatry. 2002;7(6):519. PMID: 12140770
CIN - Mol Psychiatry. 2003 Sep;8(9):770-2. PMID: 12931204
MH  - Bipolar Disorder/*genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Chi-Square Distribution
MH  - Family
MH  - Haplotypes
MH  - Humans
MH  - Iowa
MH  - Maryland
MH  - Polymorphism, Single Nucleotide
MH  - Risk Factors
EDAT- 2002/07/26 10:00
MHDA- 2003/02/13 04:00
CRDT- 2002/07/26 10:00
PHST- 2001/06/03 00:00 [received]
PHST- 2001/10/02 00:00 [revised]
PHST- 2001/10/22 00:00 [accepted]
PHST- 2002/07/26 10:00 [pubmed]
PHST- 2003/02/13 04:00 [medline]
PHST- 2002/07/26 10:00 [entrez]
AID - 10.1038/sj.mp.4001058 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2002;7(6):579-93. doi: 10.1038/sj.mp.4001058.