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Biomedical subjects

Weihua Yue

Publications and source records attributed to Weihua Yue.

6 recordsLinked to original sources
PubMed2026

Contribution of copy number variants to schizophrenia in East Asian populations.

Studies on schizophrenia-associated rare copy number variants (CNVs) have predominantly focused on people of European (EUR) ancestry. Here we present a rare CNV study of schizophrenia in East Asian (EAS) populations, comprising 20,903 cases and 23,258 controls. We observed a significantly elevated genome-wide rare CNV burden in EAS cases compared with controls. Cross-population comparisons showed largely consistent rare CNV effects on schizophrenia risk. In the EAS sample, we identified nine genome-wide-significant schizophrenia-associated rare CNV loci. Meta-analysis with EUR data yielded 14 significant loci, including 8 that reached genome-wide significance for the first time. Genes within these 14 loci were significantly less tolerant to loss-of-function variants than genes in other CNV loci. The new rare CNVs associated with schizophrenia in EAS populations showed higher carrier frequencies in EAS than in EUR populations (0.38% versus 0.0017%). Overall, this study underscores the importance of increasing population diversity to fully capture the genetic underpinnings of schizophrenia.

Journal Article↗
PubMed2026

Distinct contributions of schizophrenia and neurotransmitter pathway genetic liability to neurocognition and antipsychotic efficacy in drug-naïve first-episode schizophrenia.

The genetic mechanisms underlying heterogeneity in symptom presentation and antipsychotic response in schizophrenia remain unclear, limiting the development of personalized treatment. We integrated genome-wide schizophrenia polygenic risk scores (SZ-PRS) and pathway-specific PRSs (pPRSs) for four major neurotransmitter systems to examine their associations with clinical phenotypes across the course of illness. Primary analyses were conducted in 394 drug-naïve, first-episode patients from the Chinese First-Episode Schizophrenia Trial (CNFEST) to investigate associations with baseline symptom severity, neurocognitive impairment, and longitudinal treatment response. The CNFEST cohort included 52-week longitudinal assessments of symptoms and neurocognition using the Positive and Negative Syndrome Scale and a modified version of the MATRICS Consensus Cognitive Battery. An independent case-control cohort evaluated associations with schizophrenia diagnosis, while a cohort of 514 healthy adults assessed whether PRS-cognition associations are specific to schizophrenia. Higher SZ-PRS predicted schizophrenia diagnosis (OR = 2.28, Pfdr = 0.003) and poorer baseline executive function (β = -0.44, Pfdr = 0.006) and working memory (β = -0.49, Pfdr = 0.018), but these associations were absent in healthy adults. In contrast, pPRSs showed weaker associations with diagnosis and baseline cognition but were more informative for treatment outcomes: higher serotonin-pPRS predicted greater improvement in depressive symptoms (Pfdr = 0.023-0.032), and higher GABA-pPRS predicted greater improvement in overall symptoms (Pfdr = 0.038-0.043) during weeks 4-24. Exploratory drug-specific analyses further suggested that treatment response varied across antipsychotics and was differentially associated with pPRSs. These findings demonstrate that genome-wide and pathway-specific PRSs contribute distinctly to schizophrenia phenotypes, supporting their integration for personalized stratification and treatment.

Humans↗
PubMed2026

B cell pathways implicate shared genetic architecture between schizophrenia and immune-mediated diseases.

BACKGROUND: Schizophrenia and immune-mediated diseases are globally prevalent and highly heritable conditions that frequently co-occur, posing major public health burdens. However, their shared genetic architecture remains poorly understood. METHODS: We applied the bivariate causal mixture model (MiXeR) to investigate the polygenic overlap between schizophrenia and eight common immune-mediated diseases, using genome-wide association study summary statistics comprising 2,489 to 67,323 cases and 9,066 to 497,622 controls. Shared loci were identified through conditional/conjunctional false discovery rate (cond/conjFDR), local genetic correlation (LAVA), and colocalization analyses. Subsequently, gene mapping, functional annotation, expression-trait association, and drug-gene interaction analyses were performed to explore shared genes and enriched pathways, and genetic risk scores (GRS) from the UK Biobank were used to validate the findings. RESULTS: MiXeR estimated substantial polygenic overlap between schizophrenia and immune-mediated diseases, and conjFDR identified 133 shared loci, with eight prioritized through local genetic correlation and colocalization signals. These eight loci were mapped to 85 protein-coding genes enriched in pathways essential for B cell function. Among them, S-PrediXcan analyses identified 14 genes whose expression in brain tissues or blood was associated with both diseases. These genes also interact with immunomodulatory or antihypertensive drugs. Additionally, 11 of the 14 genes were linked to innate immunity and/or cognitive traits. Using UK Biobank data, we further confirmed that overall, shared gene, and B cell activation and receptor signaling pathway–specific genetic risk for schizophrenia is associated with immune-mediated disease susceptibility. CONCLUSIONS: These findings underscore the shared genetic architecture of schizophrenia and immune-mediated diseases, advancing insights at the interface of psychiatric genetics and immunology.

Schizophrenia↗
PubMed2006

Association of G72/G30 polymorphisms with early-onset and male schizophrenia.

To explore the effect of G72/G30 polymorphisms on the clinical manifestations of schizophrenia, especially on the age at onset and sex of patients, we examined three single nucleotide polymorphisms in 216 schizophrenic patients and 321 healthy controls. Significant associations of schizophrenia with the A allele of rs947267 (P=0.012) and haplotype A-A-G (rs2391191-rs947267-rs778294) (P=0.008) were found in early-onset schizophrenic patients. So did the same allele (P=0.034) and haplotype (P=0.009) as mentioned above in male patients. These findings suggest that the G72/G30 gene may modulate the age at onset and there might be a potential interaction between this locus and sex in the pathogenesis of schizophrenia.

Adult↗
PubMed2006

GM1 up-regulates Ubiquilin 1 expression in human neuroblastoma cells and rat cortical neurons.

GM1 ganglioside was reported to mediate the amyloid beta-protein (Abeta) secretion and accumulation in the pathogenesis of Alzheimer's disease (AD). The objective of this project was to comprehend the underlying molecular changes related to amyloid beta-protein precursor (APP) processing pathway induced by GM1. Using suppression subtractive hybridisation (SSH), we detected one prominent sequence with increased expression in human neuroblastoma cells that stably transfected with human APP695 cDNA treated with GM1. This transcript has high identity to human Ubiquilin 1 gene. Differential expression was initially confirmed by dot blot hybridization. This result was further authenticated with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Furthermore, using Western blots, we discovered that GM1 stimulated the expression of Ubiquilin 1 in human neuroblastoma cells and rat cortical neurons while other gangliosides Asialo-GM1 and GD1b did not. Ubiquilin 1 is one of the candidate genes of AD, which have been shown to modulate the gamma-secretase components in the proteolytic processing of APP, and is therefore a putative candidate for further investigation of GM1 mechanisms in the etiology and pathology of AD.

Adaptor Proteins, Signal Transducing↗
PubMed2003

A case-control study on psychological symptoms in sleep apnea-hypopnea syndrome.

OBJECTIVES: To investigate the psychological status of patients with sleep apnea-hypopnea syndrome (SAHS) and to evaluate the association of SAHS with psychological symptoms, using the Symptom Checklist-90 (SCL-90) scale. METHODS: The study comprised 30 SAHS patients (25 men, 5 women) and 30 matched, healthy control subjects. They all completed the SCL-90 and the Epworth Sleep Scale (ESS) and underwent a whole-night polysomnographic (PSG) examination. We used t-tests for group comparisons of nocturnal PSG characteristics, daytime sleepiness, and psychological symptoms. We employed Spearman's rank correlation analysis to indicate the effects of several nocturnal PSG variables (for example, total sleep time, percentage of wake at sleep, Apnea and Hypopnea Index [AHI], and oxygen desaturation) or subjective daytime sleepiness on psychological symptoms in SAHS. RESULTS: SAHS patients suffered from fragmented sleep and decreased arterial oxygen saturations, compared with healthy control subjects. The General Severity Index (GSI) of SCL-90 was significantly higher in SAHS patients than in healthy control subjects, as were measures of somatization, obsession-compulsion, depression, anxiety, and hostility (P < 0.05). The severity of psychological symptoms in SAHS patients was negatively related to total sleep time and percentage of stage 2 nonrapid eye movement (NREM) sleep; it was positively related to percentage of wake time after sleep onset, percentage of stage 1 NREM sleep, and ESS scores. CONCLUSION: In our study population, SAHS patients had decreased psychological well-being, which could be explained by fragmented sleep or excessive daytime sleepiness.

Adult↗