No evidence for association between NOTCH4 and schizophrenia in a large family-based and case-control association analysis.
OBJECTIVE
An analysis of 80 British parent-offspring trios by Wei and Hemmings in 2000 revealed thre1e out of five markers within the NOTCH4 locus to be strongly associated with schizophrenia. In our present study, we have examined NOTCH4 markers in large samples of German and Palestinian-Arab origin.


METHODS
Our study population comprised a German case-control sample (n=512 schizophrenia patients and n=232 controls) and two independent parent-offspring trio samples of German (n=159 trios) and Palestinian-Arab (n=208 trios) descent. We examined a total of ten single nucleotide polymorphisms within the NOTCH4 locus and the adjacent loci, spanning a region of approximately 100 kb.


RESULTS
Neither single marker nor haplotype analyses showed association with schizophrenia. In addition, analyses of the German case-control and trio samples revealed no significant association between NOTCH4 polymorphisms and early-onset schizophrenia.


CONCLUSIONS
Our results suggest that NOTCH4 is unlikely to play a major role in the genetic predisposition to schizophrenia in the German or the Palestinian-Arab population.
Ivo
Roland
R
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Schulze
Thomas G
TG
Schumacher
Johannes
J
Kesper
Kristina
K
Müller
Daniel J
DJ
Kremer
Ilana
I
Dobrusin
Michael
M
Mujaheed
Mustafa
M
Murad
Ibrahim
I
Blanaru
Monika
M
Bannoura
Isaam
I
Reshef
Alon
A
Bachner-Melman
Rachel
R
Ebstein
Richard P
RP
Propping
Peter
P
Belmaker
Robert H
RH
Maier
Wolfgang
W
Rietschel
Marcella
M
Nöthen
Markus M
MM
Cichon
Sven
S
D016022:Case-Control Studies; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch