SNX29, a new susceptibility gene shared with major mental disorders in Han Chinese population.

OBJECTIVES: Environmental and genetic factors play important roles in the development of schizophrenia (SCZ), bipolar disorder (BPD) or major depressive disorder (MDD). Some risk loci are identified with shared genetic effects on major psychiatric disorders. To investigate whether SNX29 gene played a significant role in these psychiatric disorders in the Han Chinese population. METHODS: We focussed on 11 single-nucleotide polymorphisms (SNPs) harbouring SNX29 gene and carried out case-control studies in patients with SCZ (n = 1248), BPD (n = 1344), or MDD (n = 1056), and 1248 healthy controls (HC) recruited from the Han Chinese population. We constructed weighted gene co-expression network analysis (WGCNA) and extracted significant modules by R package. RESULTS: We found that rs3743592 was significantly associated with MDD and rs6498263 with BPD in both allele and genotype distributions. Before correction, rs3743592 showed allelic and genotypic significance with SCZ, rs6498263 showed allelic significance with SCZ. WGCNA identified top 10 modules of co-expressed genes. Gene Ontology (GO) and pathway analysis were used to examine the functions of SNX29, which revealed that SNX29 was involved in the regulation of a number of biological processes, such as TGF-beta, ErbB, and Wnt signalling pathway, etc. CONCLUSIONS: Our results supported common risk factors in SNX29 might share among these three mental disorders in the Han Chinese population.

Common variants in SATB2 are associated with schizophrenia in Uygur Chinese population.

OBJECTIVE: Schizophrenia is one of the most severe mental disorders and its etiology is supposed to be an interaction between genes and environmental factors. Previous genome-wide association studies of schizophrenia have reported multiple susceptibility loci including rs6704641 in the SATB2 gene. Recently, this locus was further confirmed as a genome-wide significant locus for association with schizophrenia by trans-ancestry meta-analysis of Han Chinese and Caucasian samples. However, there is no report of genetic analysis in Uygur Chinese population, which is considered to have a combined genetic background between eastern Asia and Caucasian. This study is aimed to explore whether SATB2 gene is significantly associated with schizophrenia in Uygur Chinese population, thus providing additional evidence for elucidating the role of SATB2 gene in schizophrenia. PARTICIPANTS AND METHODS: In this study, we performed a case-control analysis focusing on seven tag single nucleotide polymorphisms located in SATB2 gene among 985 patients with schizophrenia and 1218 healthy controls recruited from the Xinjiang Province of China. RESULTS: We found that rs6704641 was significantly associated with schizophrenia in both allelic and genotypic distributions (Pallele = 0.008, Pgenotype = 0.028 after correction). In addition, rs16831466 is significantly associated with schizophrenia in allelic distributions (corrected Pallele = 0.041). Besides, several haplotypes of single nucleotide polymorphism are significantly associated with schizophrenia too. CONCLUSION: Our results suggest that SATB2 is also a susceptibility gene for schizophrenia in Uygur Chinese population, and subsequent functional experiments are necessary to reveal its role in the pathogenesis.

Genetic risk between the CACNA1I gene and schizophrenia in Chinese Uygur population.

BACKGROUND: Schizophrenia (SCZ) is a common mental disorder with high heritability, and genetic factors play a major role in the pathogenesis. Recent researches indicated that the CACNA1I involved in calcium channels probably affect the potential pathogenesis of SCZ. RESULTS: In this study, we attempted to investigate whether the CACNA1I gene contributes the risk to SCZ in the Uighur Chinese population, and performed a case-control study involving 985 patient samples and 1218 normal controls to analyze nine SNPs within the CACNA1I gene. Among these sites, six SNPs were significantly associated with SCZ in the allele distribution: rs132575 (adjusted Pallele  = 0.039, OR = 1.159), rs713860 (adjusted Pallele  = 0.039, OR = 0.792), rs738168 (adjusted Pallele  = 0.039, OR = 0.785), rs136805 (adjusted Pallele  = 0.014, OR = 1.212), rs5757760 (adjusted Pallele  = 0.042, OR = 0.873) and rs5750871 (adjusted Pallele  = 0.039, OR = 0.859). In addition, two SNPs turned to be risk factors for SCZ not only in the allele distribution, but also in the genotype distribution: rs132575 (adjusted Pgenotype  = 0.037) and rs136805 (adjusted Pgenotype  = 0.037). CONCLUSIONS: Overall, the present study provided evidence that significant association exists between the CACNA1I gene and SCZ in the Uighur Chinese population, subsequent validation of functional analysis and genetic association studies are needed to further extend this study.

Genetic analysis of common variants in the ZNF804A gene with schizophrenia and major depressive disorder.

AIM/OBJECTIVES/BACKGROUND: ZNF804A has been investigated widely as a candidate susceptibility gene for mental disorders in individuals of different ethnicities. However, in the Han Chinese population, most studies of this gene have focused on associations of the common single nucleotide polymorphism (SNP) rs1344706. METHODS: To investigate additional common variants within ZNF804A, we carried out a case-control study of 13 SNPs distributed across the whole gene, in 1330 schizophrenic patients, 1045 major depressive disorder patients, and 1235 normal controls. RESULTS AND CONCLUSIONS: We found that rs12476147 (P=0.0078) was associated significantly with schizophrenia, but no SNPs showed statistically significant associations with major depressive disorder after Bonferroni correction. Moreover, we also found that haplotype block 2, which included rs12476147 and rs1344706, was associated significantly with schizophrenia and major depressive disorder. Nevertheless, we could not replicate the association of rs1344706 with schizophrenia. In conclusion, the common variant rs12476147 and the related haplotype block in ZNF804A were associated significantly with schizophrenia in the Han Chinese population.

Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia.

We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome-wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including ∼50% that achieved nominal significance and ∼75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses. We observed improvements in the fine-mapping resolution at many susceptibility loci. Our results provide several lines of evidence supporting candidate genes at many loci and highlight some pathways for further research. Together, our findings provide novel insight into the genetic architecture and biological etiology of schizophrenia.

Association between the variability of the ABCA13 gene and the risk of major depressive disorder and schizophrenia in the Han Chinese population.

OBJECTIVES: The ATP-binding cassette transporter superfamily is one of the largest membrane protein families, which is responsible for transportation of substances across the membranes by utilising energy. Some research has bridged the variations in ABCA13 with occurrence of psychiatric disorders. To investigate the overlapping risk conferred by ABCA13 for both major depressive disorder and schizophrenia, we analysed tag single nucleotide polymorphisms (tag SNPs). METHODS: We used TaqMan® technology to genotype 1045 major depressive disorder patients, 1235 schizophrenia patients and 1235 healthy controls of Han Chinese origin. RESULTS: We found that rs7789493 (Pallele = 7.23E-04, Pgenotype =.001) was associated with major depressive disorder, while rs17132388 (Pallele = 1.63E-04, Pgenotype = 7.50E-04) and rs6583476 (Pallele = 5.50E-04, Pgenotype =.002) showed statistically significant association with schizophrenia. CONCLUSIONS: Our results indicate that the ABCA13 gene may contain overlapping common genetic risk factors for both major depressive disorder and schizophrenia in the Han Chinese population. The study on variants conferring overlapping risk for multiple psychiatric disorders could be tangible pathogenesis support in clinical or diagnostic references.

Common variants predict recurrence after nonfamilial atrial fibrillation ablation in Chinese Han population.

BACKGROUND: Genome-wide association studies (GWAS) have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between susceptibility loci and clinical recurrence of AF after catheter ablation have not been examined in Chinese Han populations. To the personalization of catheter ablation for AF, we examined whether these single nucleotide polymorphisms (SNPs) can predict clinical outcomes after catheter ablation for AF in Chinese Han population. METHODS AND RESULTS: The association between 8 SNPs and AF was studied in 1418 AF patients and 1424 controls by the unconditional logistic regression analysis. The survival analyses were used to compare AT/AF recurrence differences among 438 AF patients, which were classified by the genotype of rs2200733. rs2200733 and rs6590357 were significantly associated with AF in Chinese Han population. In addition, rs2200733 was associated with clinical recurrence of AF after catheter ablation. In Kaplan-Meier survival analysis, the recurrence-free rates for AF with TT and with TC+CC were 35.5% and 61.9%, respectively (P=0.0009). In multivariate Cox regression analysis, rs2200733 was strong independent risk factor for recurrence. CONCLUSION: rs2200733 risk allele at the 4q25 predicted impaired clinical response to catheter ablation for AF in Chinese Han population. Our findings suggested rs2200733 polymorphism may be used as a clinical tool for selection of patients for AF catheter ablation.

Genetic association between NRG1 and schizophrenia, major depressive disorder, bipolar disorder in Han Chinese population.

Schizophrenia, major depressive disorder, and bipolar disorder are three major psychiatric disorders affecting around 0.66%, 3.3%, and 1.5% of the Han Chinese population respectively. Several genetic linkage analyses and genome wide association studies identified NRG1 as a susceptibility gene of schizophrenia, which was validated by its role in neurodevelopment, glutamate, and other neurotransmitter receptor expression regulation. To further investigate whether NRG1 is a shared risk gene for major depressive disorder, bipolar disorder as well as schizophrenia, we performed an association study among 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls. Totally 15 tag SNPs were genotyped and analyzed, and no population stratification was found in our sample set. Among the sites, rs4236710 (corrected Pgenotye = 0.015) and rs4512342 (Pallele = 0.03, Pgenotye = 0.045 after correction) were associated with schizophrenia, and rs2919375 (corrected Pgenotye = 0.004) was associated with major depressive disorder. The haplotype rs4512342-rs6982890 showed association with schizophrenia (P = 0.03 for haplotype "TC" after correction), and haplotype rs4531002-rs11989919 proved to be a shared risk factor for both major depressive disorder ("CC": corrected P = 0.009) and bipolar disorder ("CT": corrected P = 0.003). Our results confirmed that NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population.

Analysis of association between common variants in the SLCO6A1 gene with schizophrenia, bipolar disorder and major depressive disorder in the Han Chinese population.

OBJECTIVES: The SLCO6A1 gene belongs to a superfamily of genes which is known to be a solute carrier family of OATPs (SLCO). The SLCO6A1 gene encodes OATP6A1 protein in humans. A previous genome-wide association study (GWAS) of schizophrenia conducted in the Swedish population demonstrated a significant association of rs6878284, which is located in the SLCO6A1 gene, with schizophrenia. To further investigate whether this gene is also a risk locus for schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD) in the Han Chinese population, a case-control study was designed. METHODS: In total 1,248 unrelated SCZ cases, 1,344 BPD cases, 1,056 unrelated MDD cases and 1,248 normal controls were analysed in this study. We genotyped five SNPs using the Sequenom MassARRAY platform. RESULTS: We found no association of rs6878284 with SCZ [Corrected Pallele = 0.969, Corrected Pgenotype = 0.997]. Furthermore, we found a statistically significant association of the rs7734060 genotype with MDD after correction [rs7734060: Corrected Pallele = 0.114, Corrected Pgenotype = 0.036] in the Han Chinese population. CONCLUSIONS: This is the first study which reveals no association of rs6878284 with SCZ and also predicts that rs7734060 could be a risk locus for MDD in the Han Chinese population.

Polymorphisms in NRGN are associated with schizophrenia, major depressive disorder and bipolar disorder in the Han Chinese population.

BACKGROUND: The NRGN gene locates on 11q24 and encodes a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. In a previous genome-wide association study of schizophrenia in the Caucasian population, rs12807809 of NRGN was found to be significantly associated with schizophrenia, moreover, it was further found to be associated with bipolar disorder. METHODS: We recruited 1248 schizophrenia cases, 1344 bipolar disorder cases, 1056 major depressive disorder cases, and 1248 healthy controls from Han Chinese population. Rs12807809 and another two tag SNPs of NRGN were genotyped and analyzed in three diseases respectively. A meta-analysis of rs12807809 was also conducted to verify its association with schizophrenia in Han Chinese population. RESULTS: Rs7113041 was associated with bipolar disorder (odds ratio, 95% confidence interval (OR, 95% CI)=1.194, 1.032-1.383; Pgenotype=0.0126), and rs12278912 was associated with major depressive disorder (OR, 95% CI=0.789, 0.673-0.924; Pallele=0.0102, Pgenotype=0.0399) after Bonferroni correction. The "GA" haplotype of rs7113041-rs12278912 was significantly associated with schizophrenia, major depressive disorder and bipolar disorder (corresponding P values were 2.85E-04, 3.00E-03, and 5.40E-04 after Bonferroni correction). LIMITATIONS: Despite the association between NRGN and psychoses we have found, we failed to validate the positive variant rs12807809, which was reported in the Caucasian genome-wide association study both in our single site association test and the meta-analysis. Functional studies are needed to illuminate the role of NRGN in the pathogenesis of these mental disorders. CONCLUSIONS: Our findings prove that NRGN is a shared susceptibility gene of schizophrenia, major depression and bipolar disorder in Han Chinese, and this might provide a new target for the diagnosis and treatment of these mental disorders.

Genome-wide Analysis of the Role of Copy Number Variation in Schizophrenia Risk in Chinese.

BACKGROUND: Compelling evidence suggested the role of copy number variations (CNVs) in schizophrenia susceptibility. Most of the evidence was from studies in populations with European ancestry. We tried to validate the associated CNV loci in a Han Chinese population and identify novel loci conferring risk of schizophrenia. METHODS: We performed a genome-wide CNV analysis on 6588 patients with schizophrenia and 11,904 control subjects of Han Chinese ancestry. RESULTS: Our data confirmed increased genome-wide CNV (>500 kb and <1%) burden in schizophrenia, and the increasing trend was more significant when only >1 Mb CNVs were considered. We also replicated several associated loci that were previously identified in European populations, including duplications at 16p11.2, 15q11.2-13.1, 7q11.23, and VIPR2 and deletions at 22q11.2, 1q21.1-q21.2, and NRXN1. In addition, we discovered three additional new potential loci (odds ratio >6, p < .05): duplications at 1p36.32, 10p12.1, and 13q13.3, involving many neurodevelopmental and synaptic related genes. CONCLUSIONS: Our findings provide further support for the role of CNVs in the etiology of schizophrenia.

Common variants in QPCT gene confer risk of schizophrenia in the Han Chinese population.

Schizophrenia (SCZ) is a common and severe mental disorder, its etiology has not been elucidated completely. In one previous genome-wide association study (GWAS) of SCZ in the Caucasian population, the QPCT has been reported as susceptible gene for SCZ. The QPCT gene encodes Glutaminyl cyclase (QC), an enzyme which is involved in the post translational modification by converting N-terminal glutamate of protein to pyroglutamate, which is resistant to protease degradation, more hydrophobic, and prone to aggregation and neurotoxic. To further investigate the role of this gene in the pathogenesis of schizophrenia in the Han Chinese population, we conducted this study in 1,248 (Mean age ± S.D, 36.44 years ± 9.0) SCZ cases, 1,248 (Mean age ± S.D, 30.62 years ± 11.35) healthy control samples for a case control study. We genotyped six SNPs in this study, including one positive SNP of the previous study, using the Sequenom MassARRAY platform. We found that rs2373000 was significantly associated with SCZ before correction [rs2373000: P allele = 0.016, χ(2) = 5.784, OR [95%CI] = 0.861 [0.762-0.972], P genotype = 0.018, χ(2) = 0.069]. After permutation correction for multiple testing, rs2373000 [rs2373000: P Allele corrected = 0.063, P genotype corrected = 0.069] showed marginal association with SCZ. Additionally, one pathogenic haplotype (TGT) containing rs2373000 was also significantly associated with SCZ. Our results are consistent with the findings of previous study and the genetic risk of QPCT gene for SCZ also exists in the Han Chinese population.

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.

A new risk locus in the ZEB2 gene for schizophrenia in the Han Chinese population.

The ZEB2 gene encodes the Zinc Finger E-box binding protein. As a key regulator of epithelial mesenchymal differentiation, ZEB2 plays an important role in the pathogenesis of cancer, and its high level expression has been observed in glioma patients. Different mutations in this gene have been identified in patients with Mowat-Wilson syndrome. A previous genome-wide association study (GWAS) of schizophrenia conducted in Caucasians has shown a significant association of rs12991836, located near the ZEB2 gene, with schizophrenia. Thus, we conducted a case control study to further investigate whether this genomic region is also a susceptibility locus for schizophrenia in the Han Chinese population. In total, 1248 schizophrenia (SCZ) cases (mean age±S.D., 36.44±9.0years), 1344 bipolar disorder (BPD) cases (mean age±S.D., 34.84±11.44years), 1056 major depressive disorder (MDD) cases (mean age±S.D., 34.41±12.09years) and 1248 healthy control samples (mean age±S.D., 30.62±11.35years) were recruited. We genotyped 12 SNPs using the Sequenom MassARRAY platform in this study. We found that rs6755392 showed a significant association with SCZ (rs6755392: adjusted Pallele=0.016; adjusted Pgenotype=0.052; OR (95% CI)=1.201 (1.073~1.344)). Additionally, two haplotypes (TCTG, TCTA) were also significantly associated with SCZ. This is the first study claiming the association of the genetic risks of rs6755392 in the ZEB2 gene with schizophrenia.

Noninvasive fetal trisomy detection by multiplexed semiconductor sequencing: a barcoding analysis strategy.

Noninvasive prenatal detection of fetal chromosomal aneuploidies by high-throughput next-generation sequencing proves to be accurate and sensitive. Currently, most of the data analysis methods involve a Z-score test based on the reference distribution of at least dozens of normal samples. This is not only costly but also time consuming. Moreover, as the experimental condition varies between every single run, noises cannot be eliminated and will skew the results. In order to overcome these drawbacks, we have proposed a new analytical strategy based on the multiplex barcoding sequencing of both normal and unknown samples in a single run on Ion Torrent PGM. In this method, only one normal sample is required. By applying this method to 13 single runs with a total number of 44 samples, we achieved the sensitivity and specificity of 100 and 95.181% for T13 detection, 100 and 100% for T18 detection, 90 and 100% for T21 detection, respectively.

Polymorphisms in GCKR, SLC17A1 and SLC22A12 were associated with phenotype gout in Han Chinese males: a case-control study.

BACKGROUND: Gout is a common arthritic disease resulting from elevated serum uric acid (SUA) level. A large meta-analysis including 28,141 individuals identified nine single nucleotide polymorphisms (SNPs) associated with altered SUA level in a Caucasian population. However, raised SUA level alone is not sufficient for the development of gout arthritis and most of these SNPs have not been studied in a Han Chinese population. Here, we performed a case-control association analysis to investigate the relationship between these SUA correlated SNPs and gout arthritis in Han Chinese. METHODS: A total of 622 ascertained gout p9atients and 917 healthy controls were genotyped. Genome-wide significant SNPs, rs12129861, rs780094, rs734553, rs742132, rs1183201, rs12356193, rs17300741 and rs505802 in the previous SUA study, were selected for our analysis. RESULTS: No deviation from the Hardy-Weinberg equilibrium was observed either in the case or control cohorts (corrected p > 0.05). Three SNPs, rs780094 (located in GCKR, corrected p = 1.78E(-4), OR = 0.723), rs1183201 (located in SLC17A1, corrected p = 1.39E(-7), OR = 0.572) and rs505802 (located in SLC22A12, corrected p = 0.007, OR = 0.747), were significantly associated with gout on allelic level independent of potential cofounding traits. While the remaining SNPs were not replicated. We also found significant associations of uric acid concentrations with these three SNPs (rs780094 in GCKR, corrected p = 3.94E(-5); rs1183201 in SLC17A1, corrected p = 0.005; rs505802 in SLC22A12, corrected p = 0.003) and of triglycerides with rs780094 (located in GCKR, corrected p = 2.96E(-4)). Unfortunately, SNP-SNP interactions for these three significant SNPs were not detected (rs780094 vs rs1183201, p = 0.402; rs780094 vs rs505802, p = 0.434; rs1183201 vs rs505802, p = 0.143). CONCLUSIONS: Three SUA correlated SNPs in Caucasian population, rs780094 in GCKR, rs1183201 in SLC17A1 and rs505802 in SLC22A12 were confirmed to be associated with gout arthritis and uric acid concentrations in Han Chinese males. Considering genetic differences among populations and complicated pathogenesis of gout arthritis, more validating tests in independent populations and relevant functional experiments are suggested in future.

The GSK3B gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population.

BACKGROUND: Glycogen synthease kinase-3B is a key gene encoding a protein kinase which is abundant in brain, and is involved in signal transduction cascades of neuronal cell development and energy metabolism. Previous researches proposed GSK3B as a potential region for schizophrenia. METHOD: To validate the susceptibility of GSK3B to major depressive disorder, and to investigate the overlapping risk conferred by GSK3B for mental disorders, we performed a large-scale case-control study, analyzed 6 tag single nucleotide polymorphisms using TaqMan® technology in 1,045 major depressive disorder patients, 1,235 schizophrenia patients and 1,235 normal controls of Han Chinese origin. RESULTS: We found rs334535 (Pallele=2.79E-03, Pgenotype=5.00E-03, OR=1.429) and rs2199503 (Pallele=0.020, Pgenotype= 0.040, OR=1.157) showed association with major depressive disorder before Bonferroni correction. rs6771023 (adjusted Pallele=1.64E-03, adjusted Pgenotype=6.00E-03, OR=0.701) and rs2199503 (adjusted Pallele=0.001, adjusted Pgenotype=0.002, OR=1.251) showed significant association with schizophrenia after Bonferroni correction. rs2199503 (adjusted Pallele=1.70E-03, adjusted Pgenotype=0.006, OR=1.208) remained to be significant in the combined cases of major depressive disorder and schizophrenia after Bonferroni correction. LIMITATIONS: Further validations of our findings in samples with larger scale are suggested, and functional genomic study is needed to elucidate the role of GSK3B in signal pathway and psychiatric disorders. CONCLUSIONS: Our results provide evidence that the GSK3B gene could be a promising region which contains genetic risk for both major depressive disorder and schizophrenia in the Han Chinese population. The study on variants conferring overlapping risk for multiple psychiatric disorders could be tangible pathogenesis support and clinical or diagnostic references.

Common variants at 10p12.31, 10q21.1 and 13q12.13 are associated with sporadic pituitary adenoma.

Pituitary adenoma is one of the most common intracranial neoplasms, and its genetic basis remains largely unknown. To identify genetic susceptibility loci for sporadic pituitary adenoma, we performed a three-stage genome-wide association study (GWAS) in the Han Chinese population. We first analyzed genome-wide SNP data in 771 pituitary adenoma cases and 2,788 controls and then carried forward the promising variants for replication in another 2 independent sets (2,542 cases and 3,620 controls in total). We identified three new susceptibility loci below the genome-wide significance threshold (P < 5 × 10(-8)) in the combined analyses: 10p12.31 (rs2359536, P(meta) = 2.25 × 10(-10) and rs10828088, P(meta) = 6.27 × 10(-10)), 10q21.1 (rs10763170, P(meta) = 6.88 × 10(-10)) and 13q12.13 (rs17083838, P(meta) = 1.89 × 10(-8)). This study is the first GWAS to our knowledge on sporadic pituitary adenoma, and our results provide insight into the genetic basis of this disease.

The NVL gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population.

NVL (nuclear VCP (valosin containing protein)/p97-Like), a member of the AAA-ATPase (ATPases associated with various cellular activities) family, encodes a novel hTERT (human telomerase reverse transcriptase)-interacting protein NVL2 which is a telomerase component essential for holoenzyme assembly. Previous researches have reported the impacts of telomerase activity on mental illness and the potential association between NVL and major depressive disorder. To validate the susceptibility of NVL to major depressive disorder, and to investigate the overlapping risk conferred by NVL for both major depressive disorder and schizophrenia, we analyzed 9 tag single nucleotide polymorphisms (tag SNPs) using TaqMan® technology, in 1045 major depressive disorder patients, 1235 schizophrenia patients and 1235 normal controls of Han Chinese origin. We found that rs10916583 (P(allele) = 0.020, P(genotype) = 0.028, OR = 1.156) and rs16846649 (adjusted P(allele) = 0.014, P(genotype) = 0.007, OR = 0.718) were associated with major depressive disorder, while rs10916583 (adjusted P(allele) = 1.08E-02, OR = 1.213), rs16846649 (adjusted P(allele) = 7.40E-06, adjusted P(genotype) = 8.07E-05, OR = 0.598) and rs10799541 (adjusted P(allele) = 8.10E-03, adjusted P(genotype) = 0.049, OR= 0.826) showed statistically significant association with schizophrenia after Bonferroni correction. Furthermore, rs10916583 (adjusted P(allele) = 9.00E-03, adjusted P(genotype) = 3.15E-02, OR = 1.187) and rs16846649 (adjusted P(allele) = 8.92E-06, adjusted P(genotype) = 8.84E-05, OR = 0.653) remained strongly associated with the analysis of combined cases of major depressive disorder and schizophrenia after Bonferroni correction. Our results indicated that the NVL gene may contain overlapping common genetic risk factors for major depressive disorder and schizophrenia in the Han Chinese population. The roles of NVL in telomerase biogenesis were also highlighted in psychiatric pathogenesis. The study on variants conferring overlapping risk for multiple psychiatric disorders could be tangible pathogenesis support and clinical or diagnostic references.