Identification of loci associated with schizophrenia by genome-wide association and follow-up.

We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)).

Role played by the SP4 gene in schizophrenia and major depressive disorder in the Han Chinese population.

BACKGROUND: 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. AIMS: To investigate whether the SP4 gene plays a significant role in schizophrenia or MDD in the Han Chinese population. METHOD: 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. RESULTS: 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). CONCLUSIONS: Our results suggest that common risk factors in the SP4 gene are associated with schizophrenia, although not with MDD, in the Han Chinese population.

Loci with genome-wide associations with schizophrenia in the Han Chinese population.

BACKGROUND: 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. AIMS: To validate the above findings in a Han Chinese population. METHOD: 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 ancestry. RESULTS: 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. CONCLUSIONS: 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 schizophrenia.

Genetic association of ACSM1 variation with schizophrenia and major depressive disorder in the Han Chinese population.

Schizophrenia (SCZ) and major depressive disorder (MDD) are two of the most common and severe mental disorders, the etiologies of which are not yet clearly elucidated. The ACSM1 gene has been identified as a susceptibility gene for SCZ in two previous genome-wide association studies (GWAS). ACSM1 catalyzes the activation of fatty acids and plays an important role in the metabolic system. Some evidence has suggested that ACSM1 contributes to a genetic risk for MDD. The present study aimed to evaluate the common genetic risk of the ACSM1 gene in these two disorders in the Han Chinese population. In total, 1235 patients with SCZ, 1045 patients with MDD and 1235 control subjects of Chinese origin were recruited. Six single nuclear polymorphisms (SNPs) in ACSM1 were genotyped to test their associations with SCZ and MDD. SNP rs163234 was found to be significantly associated with both SCZ (permutated Pallele=1.700×10(-3), OR=1.350 [95% CI=1.152-1.581]) and MDD (permutated Pallele=4.800×10(-3), OR=1.329 [95% CI=1.127-1.567]). SNP rs433598 showed a strong association with SCZ (permutated Pallele=4.300×10(-3), OR=1.303 [95% CI=1.117-1.520]). Haplotype analysis of the blocks containing the two positive markers also revealed a significant association. This is the first study to assess the possible association of the ACSM1 gene with a genetic susceptibility for MDD. Our data are the first to suggest a positive association of the ACSM1 gene with a genetic susceptibility for SCZ and MDD in the Han Chinese population.

DNA methylation profiling in the thalamus and hippocampus of postnatal malnourished mice, including effects related to long-term potentiation.

BACKGROUND: DNA methylation has been viewed as the most highly characterized epigenetic mark for genome regulation and development. Postnatal brains appear to exhibit stimulus-induced methylation changes because of factors such as environment, lifestyle, and diet (nutrition). The purpose of this study was to examine how extensively the brain DNA methylome is regulated by nutrition in early life. RESULTS: By quantifying the total amount of 5-methylcytosine (5mC) in the thalamus and the hippocampus of postnatal malnourished mice and normal mice, we found the two regions showed differences in global DNA methylation status. The methylation level in the thalamus was much higher than that in the hippocampus. Then, we used a next-generation sequencing (NGS)-based method (MSCC) to detect the whole genome methylation of the two regions in malnourished mice and normal mice. Notably, we found that in the thalamus, 500 discriminable variations existed and that approximately 60% were related to neuronal development or psychiatric diseases. Pathway analyses of the corresponding genes highlighted changes for 9 genes related to long-term potentiation (5.3-fold enrichment, P = 0.033). CONCLUSIONS: Our findings may help to indicate the genome-wide DNA methylation status of different brain regions and the effects of malnutrition on brain DNA methylation. The results also indicate that postnatal malnutrition may increase the risk of psychiatric disorders.

CACNA1C, schizophrenia and major depressive disorder in the Han Chinese population.

BACKGROUND: Common psychiatric disorders are highly heritable, indicating that genetic factors play an important role in their aetiology. The CACNA1C gene, which codes for subunit alpha-1C of the Cav1.2 voltage-dependent L-type calcium channel, has been consistently found to be the shared risk gene for several kinds of mental disorder. AIMS: To investigate whether CACNA1C is a susceptibility gene for schizophrenia and major depressive disorder in the Han Chinese population. METHOD: We carried out a case-control study of 1235 patients with schizophrenia, 1045 with major depressive disorder and 1235 healthy controls. A tag single nucleotide polymorphism (SNP) rs1006737 along with another 10 tag SNPs in the CACNA1C gene were genotyped in all samples. RESULTS: We found that rs1006737 was associated with both schizophrenia (P(allele) = 0.0014, P(genotype) = 0.006, odds ratio (OR) = 1.384, 95% CI 1.134-1.690) and major depressive disorder (P(allele) = 0.0007, P(genotype) = 0.003, OR = 1.425, 95% CI 1.160-1.752). CONCLUSIONS: Our findings support CACNA1C being a risk gene for both schizophrenia and major depressive disorder in the Han Chinese population.

SLC17A7 gene may be the indicator of selective serotonin reuptake inhibitor treatment response in the Chinese Han population.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for major depressive disorder (MDD), although the treatment outcomes vary in different people. The vesicular glutamate transporter 1 coded by SLC17A7 gene has been reported associated with MDD. According to its role in glutamate transmission, it is reasonable to consider it as a potential pharmacogenetic candidate in SSRI treatment. A total of 290 MDD patients who had been taking SSRIs for 6 weeks were recruited. Their genotypes were assessed for the presence of 4 single-nucleotide polymorphisms, which were selected from either the HapMap Chinese ethnic group or the literature report. Treatment effects were evaluated by the change rate of Hamilton Rating Scale for Depression. After the adjustment for the false discovery rate, 1 single-nucleotide polymorphism (rs74174284, false discovery rate; P = 0.032) demonstrated significant association with SSRI treatment response at week 6. Our results suggest that genetic variants in the SLC17A7 gene may be indicators of treatment response in MDD patients treated by SSRIs.

Common variants in the CDH7 gene are associated with major depressive disorder in the Han Chinese population.

Cadherin-7 (CDH7) gene encodes a calcium dependent cell-cell adhesion glycoprotein. Gene loci of cadherins family have been supposed to be involved in the pathogenesis of psychiatric disorders. Recent genome-wide association study also demonstrated that CDH7 was significant associated with bipolar disorder. Due to the fact that the same genetic risk factor can be shared by different kinds of psychiatric disorders, we examined whether CDH7 is also associated with major depressive disorder (MDD) in this study, with a large Han Chinese sample set. We carried out a 2-stage case-control study to examine the association between CDH7 and MDD in the Han Chinese population. Ten tag SNPs were genotyped using Taqman technology in 1,045 MDD patients and 1,520 healthy controls. Single-nucleotide polymorphisms with significance were additionally genotyped in another independent sample set with 576 MDD cases and 576 healthy controls. Among ten genotyped SNPs, rs1444067 and rs12605720 was found to be significantly associated with MDD (rs1444067: P(allele) = 0.00571, OR 0.830, 95 % CI 0.728-0.947; rs12605720: P(allele) = 0.00321, OR 1.245, 95 % CI 1.076-1.441). We successfully replicated these two SNPs association with independent sample sets (rs1444067: P(allele) = 0.00518; rs12605720: P(allele) = 0.0227). Finally we have combined these results by a meta-analysis (rs1444067: P(allele) = 0.000174, OR 0.817; rs12605720: P(allele) = 0.000199, OR 1.255). Our results support CDH7 to be a risk factor of MDD in the Han Chinese population. However, further studies with more markers and independent samples were suggested to validate our findings.

The Contribution of Mosaic Chromosomal Alterations to Schizophrenia.

BACKGROUND: Mosaic chromosomal alterations (mCAs) are implicated in neuropsychiatric disorders, yet the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages is not fully established. METHODS: We analyzed blood-derived genotype arrays from 9,715 SCZ patients and 28,822 controls of Chinese descent using a computational tool (MoChA) based on long-range chromosomal information to detect mCAs. We focused on probable early developmental sCNVs through stringent filtering. We assessed the sCNVs' burden across varying cell fraction (CF) cutoffs, as well as the frequency with which genes were involved in sCNVs. We integrated this data with the Psychiatric Genomics Consortium (PGC) dataset, which comprises 12,834 SCZ cases and 11,648 controls of European descent, and complemented it with genotyping data from postmortem brain tissue of 936 subjects (449 cases and 487 controls). RESULTS: Patients with SCZ had a significantly higher somatic losses detection rate than control subjects (1.00% vs 0.52%; odds ratio (OR) = 1.91; 95% CI, 1.47-2.49; two-sided Fisher's exact test, p=1.49×10-6). Further analysis indicated that the ORs escalated proportionately (from 1.91 to 2.78) with the increment in CF cutoffs. Recurrent sCNVs associated with SCZ (OR>8; Fisher's exact test, p<0.05) were identified, including notable regions at 10q21.1 (ZWINT), 3q26.1 (SLITRK3), 1q31.1 (BRINP3) and 12q21.31-21.32 (MGAT4C and NTS) in the Chinese cohort, some regions validated with PGC data. Cross-tissue validation pinpointed somatic losses at loci like 1p35.3-35.2 and 19p13.3-13.2. CONCLUSIONS: The study highlights mCAs' significant impact on SCZ, suggesting their pivotal role in the disorder's genetic etiology.

A genome-wide association study reveals association between common variants in an intergenic region of 4q25 and high-grade myopia in the Chinese Han population.

High-grade myopia (HM) is highly heritable, and has a high prevalence in the Han Chinese population. We carried out a genome-wide association study involving 102 HM cases suffering from retinal degeneration, and 335 controls who were free from HM and fundus diseases. Significant single-nucleotide polymorphisms were replicated in two follow-up studies: stage I involved 2628 independent cases and 9485 controls, and stage II involved a further 263 cases and 586 HM-free controls. The results were combined in a meta-analysis. Cases and controls were drawn from the Chinese Han population. A locus in an intergenic region at 4q25, within MYP11 (4q22-q27, OMIM: 609994), was found to be associated with HM (rs10034228, P(meta) = 7.70 × 10(-13), allelic odds ratio = 0.81, 95% confidence interval 0.76-0.86). There are no known genes in the region but a number of expressed sequence tags (ESTs) have been located there, one of which (BI480957) has been reported to express in the native human retinal pigment epithelium. In addition, a predicted gene was identified in this region. The gene's predicted protein sequence is highly similar to tubulin, beta 8 and beta-tubulin 4Q. Several previous studies have shown that tubulin plays an important role in eye development. Our result is compatible with a previous linkage study in the Han Chinese population (mapping in MYP11, 4q22-q27), and provides a more accurate locus for HM. Although there is insufficient evidence to indicate that expressed EST and the predicted gene play an important role in developing HM, this region merits further study as a candidate for the disease.

Histamine H4 receptor polymorphism: a potential predictor of risperidone efficacy.

Histamine interacts with histamine H4 receptor (HRH4) to impact antipsychotic response. Pharmacogenetic information about this receptor could therefore be useful in developing individualized therapy. The aim of this investigation was to clarify whether polymorphisms at human HRH4 gene alter risperidone efficacy. We genotyped 5 tag-single nucleotide polymorphisms of the HRH4 gene and analyzed their association with the reduction in Positive and Negative Syndrome Scale (PANSS) scores in a group of 113 Chinese Han patients with schizophrenia who were following an 8-week period of risperidone monotherapy. Using χ(2), analysis of variance, haplotype, and receiver operating characteristics analysis, we found that HRH4 common variant rs4483927 is significantly associated with risperidone efficacy and that its TT genotype predicts poor therapeutic response both on the positive, negative, and general subscales and on the total scale of PANSS scores (P = 0.017, 0.019, 0.021, and 0.002, respectively, in analysis of variance). Our results provide the first evidence that an HRH4 polymorphism may be a molecular marker for the prediction of risperidone efficacy and suggest novel pharmacologic links between HRH4 gene and treatment of schizophrenia.

Exploring off-targets and off-systems for adverse drug reactions via chemical-protein interactome--clozapine-induced agranulocytosis as a case study.

In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR) is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI), which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems) was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs.

A new locus in chromosome 2q37-qter is associated with posterior polar cataract.

PURPOSE: To study the genetic basis of autosomal dominant posterior polar cataracts in two Chinese pedigrees. MATERIALS AND METHODS: Peripheral blood samples were collected and genomic DNA was isolated. A genome-wide scan, using microsatellite markers at approximately 10-cm intervals and additional microsatellite markers for the positive region, was performed. Haplotype data were processed using Cyrillic software (version 2.1) to define the region of the disease gene. Mutation analysis was carried out for candidate genes. Sequencing data were analyzed with the software Sequence Scanner v1.0. RESULTS: A maximum two-point LOD score (Z (max)) of 2.53 and 2.03 was obtained at marker D2S125 with recombination θ = 0.00 in the two families. The possible disease genes were located at approximately 8.44-cM between the marker D2S125 and the terminal of chromosome 2q, namely, 2q37-qter. Candidate genes, such as Gamma-crystallins (CRYGA-D), septin 2 (SEPT2), aquaporin 12B (AQP12B), and chemokine orphan receptor 7 (CXCR7), were sequenced but no causative mutations were found. CONCLUSIONS: Our results suggest that an unidentified gene in chromosome 2q37-qter is associated with posterior polar cataract, which may have an implication in understanding the genetic and molecular mechanisms of cataracts.

A systematic genetic polymorphism analysis of the CYP2C9 gene in four different geographical Han populations in mainland China.

While many studies have been focused on CYP2C9*2 and *3 there was a lack of large full gene sequencing on CYP2C9, and this study was designed to fill this gap. We used direct sequencing to systematically screen genetic polymorphisms of the CYP2C9 gene including the 5' -flanking region (2kb), all exons and their adjoining intron regions and the 3' UTR in 400 unrelated healthy Chinese Han volunteers. A total of 27 different CYP2C9 polymorphisms were identified, 3 of which were novel, including one in intron 6, a synonymous variant (1137T>C, Tyr379Tyr), and a deletion mutation in the 3'UTR (1739-1740ATdel), which potentially influences the stability of CYP2C9 mRNA. We identified CYP2C9*1, *2, *3, *8, *11, and *31, of which alleles *8 was identified for the first time in Chinese population while *11 first in Asian. This is the first systematic screening of genetic polymorphisms of CYP2C9 in the Chinese Han population.

[Advances of genetics in diabetic nephropathy].

Diabetic nephropathy (DN) is one of the most serious chronic complications of diabetes mellitus. The observed incidence patterns in different ethnics and familial clustering have suggested that the genetic factor plays an important role in the development and progression of DN. This paper reviews the recent advances on genetics of DN, including candidate genes association studies, linkage studies and genome-wide association studies (GWASs). Candidate genes association studies and meta-analysis showed that a few candidate genes have been reproducibly associated with DN, such as ACE, AGT and PPARG genes. Linkage studies and genome-wide linkage studies have also identified susceptibility chromosomal loci. With the development of high-throughput sequencing and chip techniques, GWAS has become an important strategy to identify variants responsible for DN. The genetic factor has been the significant contribution to the pathobiology of DN. However, it is not the only cause of the pathobiology of DN, because the environment factor also influences the pathobiology of DN. Nonetheless, genetic studies may provide valuable information for the pathobiology of nephropathy and potential targets of its treatment.

Metabolomic profiling to identify potential serum biomarkers for schizophrenia and risperidone action.

Despite recent advances in understanding the pathophysiology of schizophrenia and the mechanisms of antipsychotic drug action, the development of biomarkers for diagnosis and therapeutic monitoring in schizophrenia remains challenging. Metabolomics provides a powerful approach to discover diagnostic and therapeutic biomarkers by analyzing global changes in an individual's metabolic profile in response to pathophysiological stimuli or drug intervention. In this study, we performed gas chromatography-mass spectrometry based metabolomic profiling in serum of unmedicated schizophrenic patients before and after an 8-week risperidone monotherapy, to detect potential biomarkers associated with schizophrenia and risperidone treatment. Twenty-two marker metabolites contributing to the complete separation of schizophrenic patients from matched healthy controls were identified, with citrate, palmitic acid, myo-inositol, and allantoin exhibiting the best combined classification performance. Twenty marker metabolites contributing to the complete separation between posttreatment and pretreatment patients were identified, with myo-inositol, uric acid, and tryptophan showing the maximum combined classification performance. Metabolic pathways including energy metabolism, antioxidant defense systems, neurotransmitter metabolism, fatty acid biosynthesis, and phospholipid metabolism were found to be disturbed in schizophrenic patients and partially normalized following risperidone therapy. Further study of these metabolites may facilitate the development of noninvasive biomarkers and more efficient therapeutic strategies for schizophrenia.

The ENPP1 K121Q polymorphism is not associated with type 2 diabetes or obesity in the Chinese Han population.

Type 2 diabetes (T2D) mellitus is a metabolic disorder characterized by chronic hyperglycemia and insulin resistance. It has been a worldwide public health problem, which is increasing rapidly, especially in developing countries such as China. The ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene, also known as plasma cell membrane glycoprotein 1, has been reported by genetic association studies as being associated with T2D and obesity in various populations, such as Caucasian and African American. However, there are also some controversial results in Asian populations. Our study tried to examine the associations between ENPP1 and T2D and obesity. Rs1044498 (K121Q) and rs7754561 were genotyped in 1912 patients and 2041 control subjects through TaqMan technology on the ABI7900 system. They showed no statistical association with T2D, obesity or any metabolic quantitative traits. Our meta-analysis result was consistent with it. Our study did not replicate the positive association found previously and suggested that K121Q of ENPP1 might not have a major role in the susceptibility to T2D or obesity in the Chinese Han population.

An Arg124His mutation in TGFBI associated to Avellino corneal dystrophy in a Chinese pedigree.

PURPOSE: To identify the gene mutation underlying Avellino corneal dystrophy in a four-generation Chinese pedigree. METHODS: Patients from the affected family underwent detailed clinical examination involving slit-lamp photography and confocal microscopy. Genomic DNA extracted from peripheral leukocytes was amplified using touch-down PCR for gene scanning. Two-point linkage analysis and haplotyping were performed to map the relevant chromosome region. The candidate gene in this region was sequenced to screen out the disease-causing mutation. RESULTS: Patients in the pedigree were diagnosed with Avellino corneal dystrophy. Using linkage analysis, the responsible gene was mapped to chromosome 5q31.2 with a maximum LOD (log odds) score (Z(max)) of 3.23 at D5S479 (θ(max)=0.0). Haplotypes constructed from 11 microstallite markers identified the disease-linked chromosome region as being below D5S808. Sequencing of TGFBI (transforming growth factor-beta induced gene), a known gene in this region, revealed a heterozygous transition (c.418 G>A) in exon 4 resulting in Arg124His (R124H) being co-segregated with the disease in affected family members but not in the unaffected members or the 50 unrelated controls. CONCLUSIONS: Our study demonstrated that a G>A transition in Arg124His of TGFBI was responsible for Avellino corneal dystrophy in a Chinese pedigree. This result further supports the importance of TGFBIp in maintaining transparency of the cornea.

CTLA-4 confers a risk of recurrent schizophrenia, major depressive disorder and bipolar disorder in the Chinese Han population.

Previous studies have reported that the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene, which is related to immunological function such as T-cell regulation, is associated with psychiatric disorders. In this study, we studied the relationship between CTLA-4 and three major psychiatric disorders, schizophrenia, major depressive disorder and bipolar disorder in the Chinese Han population. We recruited 1140 schizophrenia patients, 1140 major depressive disorder patients, 1140 bipolar disorder patients, and 1140 normal controls to examine the risk conferred by 6 tag SNPs (rs231777, rs231775, rs231779, rs3087243, rs5742909, rs16840252) in the CTLA-4 gene. We found that rs231779 conferred a risk for schizophrenia (P(allele)=0.0003, P(genotype)=0.0016), major depressive disorder (P(allele)=0.0006, P(genotype)=0.0026) and bipolar disorder (P(allele)=0.0004, P(genotype)=0.0018). In addition, rs231777 and rs16840252 had a significant association with schizophrenia (rs231777: P(allele)=0.0201, rs16840252: P(allele)=0.0081, P(genotype)=0.0117), and rs231777 had significant association with bipolar disorder (rs231777: P(allele)=0.0199). However, after 10,000 permutations, only rs231779 remained significant (schizophrenia: P(allele)=0.0010, P(genotype)=0.0145, major depressive disorder: P(allele)=0.0010, P(genotype)=0.0201, bipolar disorder: P(allele)=0.0008, P(genotype)=0.0125). Our results suggest that shared common risk factors for schizophrenia, major depressive disorder and bipolar disorder exist in the CTLA-4 gene in the Chinese Han population.

No association of the YWHAE gene with schizophrenia, major depressive disorder or bipolar disorder in the Han Chinese population.

YWHAE is a gene encoding 14-3-3epsilon, which is highly conserved across species, from bacteria to humans, and binds to phosphoserine/phosphothreonine motifs in a sequence-specific manner. YWHAE has been reported to be associated with schizophrenia in a study based on the Japanese population. Here, we conducted a genetic association analysis between common SNPs in the YWHAE gene and psychiatric diseases including schizophrenia, major depressive disorder and bipolar disorder in Han Chinese samples (1140 schizophrenia cases, 1140 major depressive disorder cases, 1140 bipolar disorder cases and 1140 normal controls). We studied 11 SNPs, seven of which had previously been reported as significant, in YWHAE. No association was found with schizophrenia, major depressive disorder or bipolar disorder. Considering the size of our sample sets (power > 90%), our results suggest that the YWHAE does not play a major role in schizophrenia, major depressive disorder or bipolar disorder in the Han Chinese population.