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Psychiatric disorders such as schizophrenia and major depressive disorder
(MDD) are likely to be caused by multiple susceptibility genes, each with
small effects in increasing the risk of illness. Identifying DNA variants
associated with schizophrenia and MDD is a crucial step in understanding
the pathophysiology of these disorders.
To investigate whether the SP4 gene plays a significant
role in schizophrenia or MDD in the Han Chinese population.
We focused on nine single nucleotide polymorphisms (SNPs) harbouring the
SP4 gene and carried out case–control studies in 1235
patients with schizophrenia, 1045 patients with MDD and 1235 healthy
controls recruited from the Han Chinese population.
We found that rs40245 was significantly associated with schizophrenia in
both allele and genotype distributions (Pallele = 0.0005, Pallele = 0.004 after Bonferroni correction; Pgenotype = 0.0023, Pgenotype = 0.0184 after Bonferroni correction). The rs6461563
SNP was significantly associated with schizophrenia in the allele
distributions (Pallele = 0.0033, Pallele = 0.0264 after Bonferroni correction).
Our results suggest that common risk factors in the SP4
gene are associated with schizophrenia, although not with MDD, in the Han
A large schizophrenia genome-wide association study (GWAS) and a
subsequent extensive replication study of individuals of European
ancestry identified eight new loci with genome-wide significance and
suggested that the MIR137-mediated pathway plays a role
in the predisposition for schizophrenia.
To validate the above findings in a Han Chinese population.
We analysed the single nucleotide polymorphisms (SNPs) in the newly
identified schizophrenia candidate loci and predicted
MIR137 target genes based on our published Han
Chinese populations (BIOX) GWAS data. We then analysed 18 SNPs from the
candidate regions in an independent cohort that consisted of 3585
patients with schizophrenia and 5496 controls of Han Chinese
We replicated the associations of five markers
(P<0.05), including three that were located in the
predicted MIR137 target genes. Two loci
(ITIH3/4: rs2239547, P
=1.17×10–10 and CALN1: rs2944829,
P=9.97×10–9) exhibited genome-wide
significance in the Han Chinese population.
The ITIH3/4 locus has been reported to be of genome-wide
significance in the European population. The successful replication of
this finding in a different ethnic group provides stronger evidence for
the association between schizophrenia and ITIH3/4. We
detected the first genome-wide significant association of schizophrenia
with CALN1, which is a predicted target of
MIR137, and thus provide new evidence for the
associations between MIR137 targets and
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