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

A novel model of estimating sea state bias based on multi-layer neural network and multi-source altimeter data

In this article, we propose a novel model for estimating sea state bias (SSB) based on multi-layer neural network and multi-source altimeter data from the Topex/Poseidon (T/P), Jason-2, and Jason-3 altimeters. Significant wave height (SWH), wind speed (U) and backscatter coefficient (σ0) are considered as the inputs of the multi-layer neural network, while the corresponding SSB as outputs. The neural network has four layers, with structure 3-3-6-1. Data from three seasons are employed for the neural network training, and the trained model is applied for the SSB estimation on the HY-2 altimeter data. To show the effectiveness of the adopted model, the correlations between SSB and SWH, U and σ0 are analyzed. Moreover, the explained variance and residual error are compared with a conventional parametric model for SSB estimation. The results demonstrate that multi-layer neural network trained on multi-source altimeter data performs superior to the conventional SSB estimation model

Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury

Oligodendrocyte-myelin glycoprotein (OMgp) is a myelin component that has been shown in vitro to inhibit neurite outgrowth by binding to the Nogo-66 receptor (NgR1)/Lingo-1/Taj (TROY)/p75 receptor complex to activate the RhoA pathway. To investigate the effects of OMgp on axon regeneration in vivo, OMgp-/- mice on a mixed 129/Sv/C57BL/6 (129BL6) or a C57BL/6 (BL6) genetic background were tested in two spinal cord injury (SCI) models - a severe complete transection or a milder dorsal hemisection. OMgp-/- mice on the mixed 129BL6 genetic background showed greater functional improvement compared to OMgp+/+ littermates, with increased numbers of cholera toxin B-labeled ascending sensory axons and 5-HT+ descending axons and less RhoA activation after spinal cord injury. Myelin isolated from OMgp-/- mice (129BL6) was significantly less inhibitory to neurite outgrowth than wild-type (wt) myelin in vitro. However, OMgp-/- mice on a BL/6 genetic background showed neither statistically significant functional recovery nor axonal sprouting following dorsal hemisection

Genetic risk of clozapine-induced leukopenia and neutropenia:a genome-wide association study

BACKGROUND: Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN). METHODS: A total of 1879 patients (225 CIL cases, including 43 CIN cases, and 1,654 controls) of Chinese descent were included. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC). RESULTS: The authors identified several novel loci reaching the threshold of genome-wide significance level (P < 5 × 10(−8)). Three novel loci were associated with CIL while six were associated with CIN, and two T cell related genes (TRAC and TRAT1) were implicated. The authors also observed that one locus with evidence close to genome-wide significance (P = 5.08 × 10(−8)) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis. CONCLUSIONS: The associations provide novel and valuable understanding of the genetic and immune causes of CIL and CIN, which is useful for improving clinical management of clozapine related treatment for schizophrenia. Causal variants and related underlying molecular mechanisms need to be understood in future developments

Common variants on 8p12 and 1q24.2 confer risk of schizophrenia

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Schizophrenia is a severe mental disorder affecting ∼1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 × 10(-10)) and 1q24.2 (rs10489202, P = 9.50 × 10(-9)). Our findings provide new insights into the pathogenesis of schizophrenia.973 Program 2010CB529600 2009AA022701 2006AA02A407 Natural Science Foundation of China 81130022 81121001 31000553 Foundation for the Author of National Excellent Doctoral Dissertation of China 201026 Program for New Century Excellent Talents in University NCET-09-0550 Shanghai Municipal Health Bureau 2008095 Shanghai Changning Health Bureau 2008406002 Shanghai Municipal Commission 09DJ1400601 National Key Technology RD Program 2006BAI05A09 Shanghai Leading Academic Discipline Project 20