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Partial directed coherence (PDC), which is capable of estimating directed brain networks in the frequency domain, has been widely used in various physiological recordings such as electroencephalograms (EEGs) and functional magnetic resonance imaging. However, clinical data from EEGs are inevitably contaminated with unexpected outlier artifacts. This will result in biased networks, which are different from the original physiological mechanism because of the L2 norm structure utilized in PDC to estimate the directed links. In this work, we define a new PDC model in the Lp norm (p ≤ 1) space to restrict outlier influence and use a feasible iteration procedure to solve this model for directed network construction. The quantitative evaluation using a predefined simulation network demonstrates that Lp-PDC is more consistent with the predefined networks than LS-PDC and Lasso-PDC under various simulated outlier conditions. Applying the Lp-PDC model to resting-state EEGs with ocular artifacts also show that the proposed PDC can effectively restrict the ocular artifacts to recover the networks, which is also more consistent with the physiological basis. Both simulation and real-life EEG applications demonstrate the efficiency of the proposed PDC in suppressing the influence of outliers in EEG signals, and the proposed Lp-PDC may be helpful to capture reliable causal relationships for related studies contaminated with outlier artifacts.

Granger analysis (GA) is widely used to construct directed brain networks based on various physiological recordings, such as functional magnetic resonance imaging, and electroencephalogram (EEG). However, in real applications, EEGs are inevitably contaminated by unexpected artifacts that may distort the networks because of the L2 norm structure utilized in GAs when estimating directed links. Compared with the L2 norm, the Lp ( ${p} \le \mathsf {1}$ ) norm can compress outlier effects. In this paper, an extended GA is constructed by applying the Lp ( ${p} \le \mathsf {1}$ ) norm strategy to estimate robust causalities under outlier conditions, and a feasible iteration procedure is utilized to solve the new GA model. A quantitative evaluation using a predefined simulation network demonstrates smaller bias errors and higher linkage consistence for the Lp ( ${p} = \mathsf {1.0}$ , 0.8, 0.6, 0.4, 0.2) -GAs compared with both the Lasso- and L2-GAs under various simulated outlier conditions. Applications in resting-state EEGs that contain ocular artifacts also show that the proposed GA can effectively compress the ocular outlier influence and recover the reliable networks. The proposed Lp-GA may be helpful in capturing the reliable network structure when EEGs are contaminated with artifacts in related studies.

Major depressive disorder (MDD) is a common and complex mental disorder. Recent studies found that genetic variants located in GRIK4, which encoded glutamate ionotropic receptor kainate type subunit 4, was associated with the MDD. In this study, we intended to investigate whether GRIK4 gene was associated with MDD. So five single nucleotide polymorphisms (SNPs) were selected and genotyped (rs79526501, rs11218016, rs4582985, rs6589847, rs56275759) in 568 MDD patients and 846 healthy controls from Chinese Han population. The results showed that rs56275759 demonstrated statistically significant differences between MDD patients and control subjects both in allelic frequencies (p value = 0.011) and genotypic frequencies (p value = 0.029). Rs4582985 was excluded from the further analysis for its deviation from the Hardy-Weinberg equilibrium. Strong linkage disequilibrium (LD) was found among rs11218016, rs6589847 and rs56275759, and this block was significantly associated with MDD. In summary, our results firstly indicated that rs56275759 of GRIK4 gene might be associated with MDD in Chinese Han population.

Schizophrenia is a severe and complex mental disorder with high heritability. There is evidence that mutations in the gene of Nmethyl-d-aspartate-type glutamate receptors (NMDAR) are associated with schizophrenia. GRIN2B encodes a subunit of NMDARs, and has been identified as a candidate gene for many psychiatric disorders, especially schizophrenia. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in GRIN2B were associated with schizophrenia. Four SNPs (rs890, rs1806191, rs219872, rs172677) were genotyped in 752 schizophrenic patients and 846 healthy controls of the Chinese Han population. Our results indicate differences in allele and genotype frequencies of rs890 between case and control. These results were assessed by adapting different genetic models (codominant, dominant, recessive, overdominant, log-additive models). After controlling for confounding factors including sex and age, rs890 remained associated with schizophrenia. In addition, rs890 and rs1806191 were found to form a haplotype associated with schizophrenia. In summary, our results indicate that the GRIN2B SNP rs890 might be associated with schizophrenia in the Chinese Han population.

This study was intended to ascertain whether SNPs in dopaminergic and serotoninergic pathway genes SLC6A2, SLC6A3 and DRD2 are associated with schizophrenia in Han Chinese people. We conducted a case-control study by genotyping 7 SNPs of the three genes in 1034 schizophrenia patients and 1034 controls. No significant difference in the allelic or genotypic frequency was detected between cases and controls despite one positive haplotype (rs1362621-rs2242446-rs5564). Stratified analysis of gender and gene-gene interaction analysis showed no positive results. In summary, our study denies the major role of these SNPs within the three genes for schizophrenia in Han Chinese.

Schizophrenia (SCZ) is a complex, heritable, and devastating psychiatric disorder. Mutations in the members of ABC transporters have been associated with psychiatric illnesses.In this study, we investigated whether 9 SNPs in ABCB1 (rs6946119, rs28401781, rs4148739, and rs3747802), ABCB6 (rs1109866, rs1109867, rs3731885, and rs3755047), and ABCG1 (rs182694) contribute to the risk of SCZ in a Han Chinese population.We conducted a case-control study in a Han Chinese population, involving 1,034 SCZ patients and 1,034 unrelated healthy controls to genotype 9 SNPs.The analysis demonstrated that rs182694 of ABCG1 was significantly different between SCZ patients and controls as to allele (rs182694: p = 0.0070, χ2 = 7.27) and genotype frequencies (rs182694: p = 0.0013, χ2 = 13.35).Our findings support an association between ABCG1 polymorphism and SCZ in a Han Chinese population.

Schizophrenia is a severe and complex mental disorder with high heritability. There is an evidence that metabotropic glutamate receptors (GRM) are associated with schizophrenia. GRM7 has been identified as a candidate gene for many psychiatric disorders especially schizophrenia. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in GRM7 were associated with schizophrenia. Four SNPs (rs9814881, rs13353402, rs9870680 and rs1531939) were genotyped in 1034 schizophrenic patients and 1034 healthy controls of Chinese Han origin. The results showed that the two SNPs rs13353402 and rs1531939 demonstrated significant difference between schizophrenic patients and control subjects in allele frequencies (rs13353402: P value=0.0307, rs1531939: P value=0.0328, respectively). Nevertheless, there was no significant discrepancies in genotype distribution. In summary, our results indicate that the GRM7 SNPs rs13353402 and rs1531939 might be associated with schizophrenia in 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.

Evidence has indicated that the incidence of colorectal cancer (CRC) among schizophrenia is lower than normal. To explore this potential protective effect, we employed an innovative strategy combining association study with allele-specific expression (ASE) analysis in MCC gene. We first genotyped four polymorphisms within MCC in 312 CRC patients, 270 schizophrenia patients and 270 controls. Using the MassArray technique, we performed ASE measurements in a second sample series consisting of 50 sporadic CRC patients, 50 schizophrenia patients and 52 controls. Rs2227947 showed significant differences between schizophrenia cases and controls, and haplotype analysis reported some significant discrepancies among these three subject groups. ASE values of rs2227948 and rs2227947 presented consistently differences between CRC (or schizophrenia) patients and controls. Of the three groups, highest frequencies of ASE in MCC were concordantly found in CRC group, whereas lowest frequencies of ASE were observed in schizophrenia group. Similar trends were confirmed in both haplotype frequencies and ASE frequencies (i.e. CRC > control > schizophrenia). We provide a first indication that MCC might confer alterative genetic susceptibility to CRC in individuals with schizophrenia promising to shed more light on the relationship between schizophrenia and cancer progression.

Schizophrenia (SZ) and major depressive disorder (MDD) are two common severe mental disorders that have arisen to public awareness in recent years. Serotonin (5-HT) receptors have been implicated in the pathophysiology of psychiatric disorders especially in MDD and SZ. The aim of this study is to explore whether the variants in the 5-HT1A and 5-HT2A gene are susceptible to SZ or MDD in the Chinese Han population. Five SNPs (Single Nucleotide Polymorphisms) (rs1364043, rs10042486, rs6313, rs6311, rs17289304) in these genes were genotyped from 752 SZ patients, 568 MDD patients, and 846 normal controls of Chinese Han origin. The results showed that the 5-HT1A rs10042486 was significantly associated with SZ ( P allele = 0.0369, P genotype = 0.0098). Moreover, the haplotype (C-T) composed of rs10042486 and rs1364043 showed significant difference between SZ cases and healthy controls ( P = 0.0302) while another haplotype (T-G) was significant for MDD ( P = 0.0247). Our study is the first to suggest a positive association of the 5-HT1A gene with SZ in the Han Chinese population.

The SLC6A3 and SLC6A4 genes are members of a class of neurotransmitter transporters for the release, re-uptake and recycling of neurotransmitters in synapses. SLC6A3 and SLC6A4 encode a dopamine transporter and serotonin transporter, respectively. Abnormal expression and genetic polymorphism of SLC6A3 and SLC6A4 genes may increase the risk of developing mental illness, such as schizophrenia, bipolar disorder, ADHD, and aggressive behavior in Alzheimer disease, etc. Nevertheless, association between SLC6A3, SLC6A4 genes polymorphism and schizophrenia patients have not been well studied in Han Chinese people. In this study, we examined whether single nucleotide polymorphisms (SNPs) in SLC6A3, SLC6A4 were associated with schizophrenia in Han Chinese people (893 schizophrenia patients and 611 healthy controls). No significant difference in allelic or genotypic frequency was found between schizophrenia patients and healthy controls. No positive linkage disequilibrium (LD) was detected either. No haplotypic distributions were positive. Accordingly, our study suggests that the 10 SNPs within both genes we examined do not play a major role in schizophrenia in the Han Chinese population.

Objective Bipolar disorder (BPD) is a serious and common mental disorder with high heritability. The serotonergic system is known to be implicated in the etiology of the disorder. Tryptophan hydroxylase isoform-2 (TPH2), which controls the synthesis of serotonin in the brain, has been suggested as a candidate gene for BDP. The aim of this study was to examine the association between the polymorphisms in TPH2 and BPD. Methods We conducted a case–control study by genotyping six SNPs (rs10784941, rs1386494, rs2171363, rs4760816, rs1386486, and rs1872824) in 506 bipolar patients and 507 controls of Chinese Han origin. Results rs10784941 was not in the Hardy–Weinberg equilibrium and therefore excluded from further analysis. rs1386486 and rs1872824 showed statistically significant differences between cases and controls in genotype frequencies (rs1386486: p = 0.043351; rs1872824: p = 0.016563), but no association in allele frequencies. Strong LD was found among rs1386494, rs2171363 and rs4760816, but no positive association with BPD was found for haplotypes. Conclusion Our results indicate that in the Han Chinese population TPH2 may be a potential susceptibility gene for bipolar disorder. Further studies are needed to validate this association.

Aim: Major depressive disorder is a common psychiatric disorder with worldwide prevalence. The most widely prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs). ATP-binding cassette proteins are responsible for the membrane transport of various molecules including antidepressive drugs. We investigated whether SNPs in ABCB6, ABCB1 and ABCG1 were associated with the treatment response of SSRIs. Materials & methods: A pharmacogenetic study genotyping nine SNPs was conducted in 290 major depressive disorder patients in the Chinese Han population. Allele and genotype frequencies were compared between responders and nonresponders. Results: The allele frequencies of rs28401781 and rs4148739 in ABCB1 showed significant difference between responders and nonresponders before correction (p = 0.0297 and p = 0.0359, respectively). No significant associations were detected for the ABCB6 or ABCG1 gene. Conclusion: Our results suggest that ABCB1 polymorphisms might be associated with SSRIs treatment response in the Chinese Han population. Original submitted 29 April 2013; Revision submitted 29 July 2013

Colorectal cancer (CRC), now the third most common cancer across the world, is known to aggregate in families. USP7 is a very important protein with an important role in regulating the p53 pathway, which is critical for genomic stability and tumor suppression. We here genotyped eight SNPs within the USP7 gene and conducted a case-control study in 312 CRC patients and 270 healthy subjects in the Chinese Han population. No significant associations were found for any single SNP and CRC risk. Our data eliminate USP7 as a potential candidate gene towards for CRC in the Han Chinese population.

Objectives Colorectal cancer (CRC) is a common malignancy with worldwide prevalence. Familial adenomatous polyposis (FAP), a predisposition syndrome of CRC, is caused by germ line mutations in the APC gene. Mutations in APC are thought to be an early event in colorectal tumorigenesis. We hypothesized that common variants in APC might be associated with CRC. Design and methods A case-control study genotyping ten SNPs was conducted in 312 CRC patients and 270 normal controls in the Chinese Han population. Results The genotype frequency of rs2019720 showed a significant difference between cases and controls (p = 0.046, after Bonferroni correction). For the three pairs of SNPs in strong LD, we carried out haplotype analyses but no significant association was detected. Conclusion Our results suggest that APC polymorphisms might be associated with CRC in the Chinese Han population.