f95126b6-c239-4182-b1b3-df9a3fd5355d
title
Is  NOTCH4  associated with schizophrenia?
a108035c-65e5-40c1-a194-0b1dd44a92e2
abstract
The  NOTCH4  locus was reported to be associated with schizophrenia in our previous study but the subsequent replication by other workers has been inconsistent. To find out possible reasons for the poor replication, the present work was undertaken to analyse four functional single nucleotide polymorphisms (SNPs) ( rs367398 ,  rs915894 ,  rs520692  and  rs422951 ) at the  NOTCH4  locus among 141 schizophrenic family trios of Chinese Han descent. Of these four SNPs,  rs520692  was the only one associated with schizophrenia (P = 0.017); the other three, however, did not show any association with the illness, including  rs367398  located in the promoter region, which had shown a strong association with the illness in our previous study conducted with British samples. Although these four SNPs analysed lie within a less than 4 kb segment of genomic DNA, the pattern of linkage disequilibrium between them was unexpected. The strongest linkage disequilibrium was shown only between  rs367398  and  rs520692  and between  rs520692  and  rs422951  in both parent and patient groups. This study raises the possibility that there might be two or more disease-underlying variants at the  NOTCH4  locus or at a nearby locus, and that the allelic or locus heterogeneity may be one of the possible reasons for the poor replication of the  NOTCH4  finding.