PMID- 17375136
OWN - NLM
STAT- MEDLINE
DCOM- 20080214
LR  - 20150813
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 32
IP  - 12
DP  - 2007 Dec
TI  - A large case-control study of common functional SLC6A4 and BDNF variants in 
      obsessive-compulsive disorder.
PG  - 2543-51
AB  - Both serotonin transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) 
      genes have shown positive associations with obsessive-compulsive disorder (OCD) 
      and some other psychiatric disorders, but these results have not been 
      consistently replicated. To explore the hypothesis that this variability might 
      result from the effects of differing combinations of overlooked variants within 
      SLC6A4 together with small OCD and control sample sizes, we studied three common 
      functional polymorphisms (5-HTTLPR, STin2, and the newly discovered SNP, rs25531) 
      in the largest sample size of OCD patients (N=347) and controls (N=749) ever 
      investigated. During methods development, we found evidence for potential SLC6A4 
      genotyping problems with earlier methodology, a third possible contributor to 
      variability in earlier studies. A fourth possible explanation might be SLC6A4 x 
      BDNF interactions, which prompted us to investigate combined genotypes of BDNF 
      V66M with the three SLC6A4 loci. Except for a nominal association with rs25531 
      alone, which did not survive correction for multiple comparisons, we found no 
      evidence for any of these other variants being associated alone or together with 
      OCD, and we therefore also examined clinical OCD subtypes within the sample to 
      evaluate clinical heterogeneity. Subgroups based on the age of OCD onset, gender, 
      familiality, factor analysis-derived symptom dimensions, or comorbidity with 
      other psychiatric disorders failed to identify SLC6A4- or BDNF-associated 
      phenotypes, with one exception of overall number of comorbid anxiety disorders 
      being significantly associated with 5-HTTLPR/rs25531. We conclude that despite 
      their attractiveness as candidate genes in OCD, our data provide no support for 
      association in this large OCD patient sample and point toward the need to examine 
      other genes as candidates for risk determinants in OCD.
FAU - Wendland, Jens R
AU  - Wendland JR
AD  - Laboratory of Clinical Science, National Institute of Mental Health, National 
      Institutes of Health, Bethesda, MD 20892, USA. wendlandj@mail.nih.gov
FAU - Kruse, Matthew R
AU  - Kruse MR
FAU - Cromer, Kiara R
AU  - Cromer KR
FAU - Murphy, Dennis L
AU  - Murphy DL
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20070321
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (SLC6A4 protein, human)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
SB  - IM
EIN - Neuropsychopharmacology. 2008 May;33(6):1476. Cromer, Kiara C [corrected to 
      Cromer, Kiara R]
MH  - Age of Onset
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Case-Control Studies
MH  - Female
MH  - Gene Frequency/physiology
MH  - Genotype
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Obsessive-Compulsive Disorder/*genetics
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Psychiatric Status Rating Scales
MH  - Serotonin Plasma Membrane Transport Proteins/*genetics
EDAT- 2007/03/22 09:00
MHDA- 2008/02/15 09:00
CRDT- 2007/03/22 09:00
PHST- 2007/03/22 09:00 [pubmed]
PHST- 2008/02/15 09:00 [medline]
PHST- 2007/03/22 09:00 [entrez]
AID - 1301394 [pii]
AID - 10.1038/sj.npp.1301394 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2007 Dec;32(12):2543-51. doi: 10.1038/sj.npp.1301394. 
      Epub 2007 Mar 21.