The Psychiatric Genomics Consortium(PGC)has recently identified 10 potential functional coding variants for schizophrenia.However,how these coding variants confer schizophrenia risk remains largely unknown.Here,we inv...The Psychiatric Genomics Consortium(PGC)has recently identified 10 potential functional coding variants for schizophrenia.However,how these coding variants confer schizophrenia risk remains largely unknown.Here,we investigate the associations between eight potential functional coding variants identified by PGC and schizophrenia in a large Han Chinese sample(n=4022 cases and 9270 controls).Among the eight tested single nucelotide polymorphisms(SNPs),rs3617(a missense variant,p.K315 Q in the ITIH3 gene)showed genome-wide significant association with schizophrenia in the Han Chinese population(P=8.36×10-16),with the same risk allele as in PGC.Interestingly,rs3617 is located in a genomic region that is highly evolutionarily conserved,and its schizophrenia risk allele(C allele)was associated with lower ITIH3 mRNA and protein expression.Intriguingly,mouse neural stem cells stably overexpressing ITIH3 with different alleles of rs3617 exhibited significant differences in proliferation,migration,and differentiation,suggesting the impact of rs3617 on neurodevelopment.Subsequent transcriptome analysis found that the differentially expressed genes in neural stem cells stably overexpressing different alleles of rs3617 were significantly enriched in schizophrenia-related pathways,including cell adhesion,synapse assembly,MAPK and PI3 K-AKT pathways.Our study provides convergent lines of evidence suggesting that rs3617 in ITIH3 likely affects protein function and neurodevelopment and thereby confers risk of schizophrenia.展开更多
The incidence of Inactive ovaries of dairy cows in China is relatively high. There is no complete early warning system for the occurrence of ovarian quiescence in clinical cows. This test provides early warning indica...The incidence of Inactive ovaries of dairy cows in China is relatively high. There is no complete early warning system for the occurrence of ovarian quiescence in clinical cows. This test provides early warning indicators for clinical prediction of ovary cessation in dairy cows. This experiment selected blood samples of dairy cows from 60 to 90 days postpartum in the inactive ovaries group and control group. Differential proteins were selected on the basis of proteomics, three energy indexes: AST, Glu, NEFA. Four reproductive hormones: E2, P4, FSH, LH, and four differentially expressed proteins: IGFBP-2, AHSG, APO-A4, and RBP-4. Key enzyme activities: ALDOB, LDHB, ITIH3, GPX3, SPAM1, PKM2. The ELISA test kit was used to detect the content and activity of the above markers in the test bovine serum. Through correlation analysis, binary logistic regression modeling and ROC analysis, a single indicator early warning technique for APOA4 and ITIH3 was established. The early warning values were APOA4 > 28.825 μg/L and ITIH3 > 195.07 ng/L. A multi-index early warning system based on potential biomarkers of APOA4 + ITIH3 and APOA4 + ITIH3 + E2 was established. The former had an early warning value of: APOA4 > 19.55 μg/I;ITIH3 > 191.14 ng/L;the latter has an early warning value: APOA4 > 47.56 μg/L, ITIH4 > 187.80 ng/L, E2 < 69.63 ng/L.展开更多
基金equally supported by the National Natural Science Foundation of China of China(31970561 and 31722029 to X.J.L.)the National Key Research and Development Program of China(Stem Cell and Translational Research)(2016YFA0100900)+1 种基金the Innovative Research Team of Science and Technology department of Yunnan Province(2019HC004)the Key Research Project of Yunnan Province(2017FA008 to X.-J.L.)。
文摘The Psychiatric Genomics Consortium(PGC)has recently identified 10 potential functional coding variants for schizophrenia.However,how these coding variants confer schizophrenia risk remains largely unknown.Here,we investigate the associations between eight potential functional coding variants identified by PGC and schizophrenia in a large Han Chinese sample(n=4022 cases and 9270 controls).Among the eight tested single nucelotide polymorphisms(SNPs),rs3617(a missense variant,p.K315 Q in the ITIH3 gene)showed genome-wide significant association with schizophrenia in the Han Chinese population(P=8.36×10-16),with the same risk allele as in PGC.Interestingly,rs3617 is located in a genomic region that is highly evolutionarily conserved,and its schizophrenia risk allele(C allele)was associated with lower ITIH3 mRNA and protein expression.Intriguingly,mouse neural stem cells stably overexpressing ITIH3 with different alleles of rs3617 exhibited significant differences in proliferation,migration,and differentiation,suggesting the impact of rs3617 on neurodevelopment.Subsequent transcriptome analysis found that the differentially expressed genes in neural stem cells stably overexpressing different alleles of rs3617 were significantly enriched in schizophrenia-related pathways,including cell adhesion,synapse assembly,MAPK and PI3 K-AKT pathways.Our study provides convergent lines of evidence suggesting that rs3617 in ITIH3 likely affects protein function and neurodevelopment and thereby confers risk of schizophrenia.
文摘The incidence of Inactive ovaries of dairy cows in China is relatively high. There is no complete early warning system for the occurrence of ovarian quiescence in clinical cows. This test provides early warning indicators for clinical prediction of ovary cessation in dairy cows. This experiment selected blood samples of dairy cows from 60 to 90 days postpartum in the inactive ovaries group and control group. Differential proteins were selected on the basis of proteomics, three energy indexes: AST, Glu, NEFA. Four reproductive hormones: E2, P4, FSH, LH, and four differentially expressed proteins: IGFBP-2, AHSG, APO-A4, and RBP-4. Key enzyme activities: ALDOB, LDHB, ITIH3, GPX3, SPAM1, PKM2. The ELISA test kit was used to detect the content and activity of the above markers in the test bovine serum. Through correlation analysis, binary logistic regression modeling and ROC analysis, a single indicator early warning technique for APOA4 and ITIH3 was established. The early warning values were APOA4 > 28.825 μg/L and ITIH3 > 195.07 ng/L. A multi-index early warning system based on potential biomarkers of APOA4 + ITIH3 and APOA4 + ITIH3 + E2 was established. The former had an early warning value of: APOA4 > 19.55 μg/I;ITIH3 > 191.14 ng/L;the latter has an early warning value: APOA4 > 47.56 μg/L, ITIH4 > 187.80 ng/L, E2 < 69.63 ng/L.
