Fei Xu

Allele-specific expression of mutated in colorectal cancer ( MCC ) gene and alternative susceptibility to colorectal cancer in schizophrenia

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. CRCu2009>u2009controlu2009>u2009schizophrenia). 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.

Association study of NOS1 gene polymorphisms with the risk of schizophrenia in Chinese Han origin

To the editor It is known that the schizophrenia (SZ) is resulted from genetic predisposition and environment factors, and the heritability is estimated at about 80% with the evidence in family and twin studies (Cardno and Gottesman, 2000). A lot of genetic association studies about SZ with candidate genes have been performed. Recently, Neuronal nitric oxide synthase (NOS1) was considered as a genetic risk factor for SZ due to the significant polymorphisms associated with SZ. Furthermore, the linkage analysis revealed that schizophrenia was significantly linked to 12q22-24 (Reif et al., 2006), on which is NOS1 gene. In this study, we investigated whether NOS1 is associated with SZ in the Chinese Han population by examining seven new SNPs between schizophrenic patients and healthy controls. A total of 2068 persons participated in this study, including 1034 unrelated Han Chinese patients with schizophrenia (625 males and 409 females, age: 45.06 ± 12.88, onset age: 25.98 ± 9.65) and 1034 controls (588 males and 446 females, age: 34.06 ± 10.00). Each patient was diagnosed by two professional psychiatrists through DSM-IV criteria. Subjects in controls would be excluded if they have psychiatry disorder or drug abuse history in the first or second degree relatives. All of these participants have signed a formal informed consent. This research was supported by the Ethics Committee of the Human Genetics Center in Shanghai. DNA was extracted from peripheral blood based on phenol-chloroform method. Given to the minor allele frequency(MAF) should be more than 0.05, we selected seven SNPs in NOS1 (rs1105026, rs9658501, rs3741475, rs1047735, rs11068428, rs1123425, rs2293054). Herein, we use MassARRAY® Analyzer 4 platform (Sequenom, CA, USA) to genotype all SNPs. Statistical analysis was performed on SHSsis (http://analysis.bio-x.cn/myAnalysis.php) (Yong and Lin, 2005). For all above analyses, P values were two tailed and the significance level was set to 0.05. Then we used the R(version 3.2.2) to assess genetic models and each genetic model was adjusted by gender and province. All of the SNPs were in Hardy-Weinberg equilibrium except rs2293054, so it would be excluded in further analysis. Only rs1123425 had a significant association with SZ in genotype frequency (rs1123425: P=0.017). Rs9658501-rs3741475 and rs1047735-rs11068428 were revealed as two blocks with strong LD (D > 0.9). However, there is no significant association between these two blocks and SZ. For rs1123425, logistic regression tests showed that rs1123425 can adopt codominant and recessive models after adjusted by gender and province (codominant model: P=0.0295, GA vs GG: OR=0.95, CI=0.77–1.18, AA vs GG: OR=1.35, CI=1.02–1.78; recessive model: P=0.0088, GG/GA vs AA: OR=1.39, CI=1.09– 1.77). Rs1123425, which is located in the intron region of NOS1 gene, was first found to have a slight association with SZ. Levels of NOS1 protein differ in the distribution between SZ and healthy controls (AKYOL et al., 2004). So we would speculate that rs1123425 might affect the mRNA level of NOS1 and alter the amount of proteins. Although there is no further evidence to prove our result, many studies have shown that polymorphisms in NOS1 are associated with the cognitive disorder in SZ. For example, in an association study between SZ patients and healthy controls, the risk G allele of rs6490121 was revealed to have an effect on verbal IQ and working memory (Donohoe et al., 2009). There are some limitations in this study, owing to the slight significant association result, we did not give a False Discovery Rate (FDR) or Bonferroni correction. Samples need to be enlarged for better analysis. And we also need further functional studies to confirm this result. In conclusion, our result support the hypothesis that NOS1 as a candidate gene for SZ in Chinese Han population.

Association study of TPH2 polymorphisms and bipolar disorder in the Han Chinese population.

OBJECTIVEnBipolar 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.nnnMETHODSnWe 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.nnnRESULTSnrs10784941 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.nnnCONCLUSIONnOur 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.

Association study between ABCB1, ABCB6 and ABCG1 polymorphisms and major depressive disorder in the Chinese Han population

Please cite this article as: Gaini Ma , Xiaoye Huang , Yan Bi , Decheng Ren , Fei Xu , Qianqian Sun , Rui Zhang , Jiaxin Hu , Weibo Niu , Zhenming Guo , Ruixue Yuan , Fan Yuan , Xi Wu , Yanfei Cao , Fengping Yang , Lu Wang , Weidong Li , Tao Yu , Lin He , Jie Liu , Guang He , Xingwang Li , Association study between ABCB1, ABCB6 and ABCG1 polymorphisms and major depressive disorder in the Chinese Han population , Psychiatry Research (2018), doi: 10.1016/j.psychres.2018.05.045

No association of GRIK4 polymorphisms with schizophrenia in the Chinese Han population

Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Institute of Mental Health, Shanghai Jiao Tong University and Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China Correspondence to Xingwang Li, PhD, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Center, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, People’s Republic of China Tel/fax: + 86 21 6282 2491; e-mail: xwli@sjtu.edu.cn

Common variants in GRIK4 and major depressive disorder: An association study in the Chinese Han population

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.