PMID- 16736033
OWN - NLM
STAT- MEDLINE
DCOM- 20060926
LR  - 20120622
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 14
IP  - 9
DP  - 2006 Sep
TI  - A summary statistic approach to sequence variation in noncoding regions of six 
      schizophrenia-associated gene loci.
PG  - 1037-43
AB  - In order to explore the role of noncoding variants in the genetics of 
      schizophrenia, we sequenced 27 kb of noncoding DNA from the gene loci RAC-alpha 
      serine/threonine-protein kinase (AKT1), brain-derived neurotrophic factor (BDNF), 
      dopamine receptor-3 (DRD3), dystrobrevin binding protein-1 (DTNBP1), neuregulin-1 
      (NRG1) and regulator of G-protein signaling-4 (RGS4) in 37 schizophrenia patients 
      and 25 healthy controls. To compare the allele frequency spectrum between the two 
      samples, we separately computed Tajima's D-value for each sample. The results 
      showed a smaller Tajima's D-value in the case sample, pointing to an excess of 
      rare variants as compared to the control sample. When randomly permuting the 
      affection status of sequenced individuals, we observed a stronger decrease of 
      Tajima's D in 2400 out of 100,000 permutations, corresponding to a P-value of 
      0.024 in a one-sided test. Thus, rare variants are significantly enriched in the 
      schizophrenia sample, indicating the existence of disease-related sequence 
      alterations. When categorizing the sequenced fragments according to their level 
      of human-rodent conservation or according to their gene locus, we observed a wide 
      range of diversity parameter estimates. Rare variants were enriched in conserved 
      regions as compared to nonconserved regions in both samples. Nevertheless, rare 
      variants remained more common among patients, suggesting an increased number of 
      variants under purifying selection in this sample. Finally, we performed a 
      heuristic search for the subset of gene loci, which jointly produces the 
      strongest difference between controls and cases. This showed a more prominent 
      role of variants from the loci AKT1, BDNF and RGS4. Taken together, our approach 
      provides promising strategy to investigate the genetics of schizophrenia and 
      related phenotypes.
FAU - Winantea, Jane
AU  - Winantea J
AD  - Institute of Human Genetics, University of Bonn, Bonn, Germany.
FAU - Hoang, My Ngo
AU  - Hoang MN
FAU - Ohlraun, Stefanie
AU  - Ohlraun S
FAU - Rietschel, Marcella
AU  - Rietschel M
FAU - Cichon, Sven
AU  - Cichon S
FAU - Propping, Peter
AU  - Propping P
FAU - Nothen, Markus M
AU  - Nothen MM
FAU - Freudenberg, Jan
AU  - Freudenberg J
FAU - Freudenberg-Hua, Yun
AU  - Freudenberg-Hua Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060531
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DNA, Intergenic)
RN  - 0 (RGS Proteins)
RN  - 175335-35-0 (RGS4 protein)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Case-Control Studies
MH  - DNA, Intergenic
MH  - *Data Interpretation, Statistical
MH  - *Genetic Variation
MH  - Humans
MH  - Polymorphism, Single Nucleotide
MH  - Proto-Oncogene Proteins c-akt/genetics
MH  - RGS Proteins/genetics
MH  - Schizophrenia/*genetics
EDAT- 2006/06/01 09:00
MHDA- 2006/09/27 09:00
CRDT- 2006/06/01 09:00
PHST- 2006/06/01 09:00 [pubmed]
PHST- 2006/09/27 09:00 [medline]
PHST- 2006/06/01 09:00 [entrez]
AID - 5201664 [pii]
AID - 10.1038/sj.ejhg.5201664 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 2006 Sep;14(9):1037-43. doi: 10.1038/sj.ejhg.5201664. Epub 2006 
      May 31.