Biology subjects

Liu, S.-H.

Publications and source records attributed to Liu, S.-H..

3 recordsLinked to original sources

bioRxiv2017

Weighted burden analysis of exome-sequenced case-control sample implicates synaptic genes in schizophrenia aetiology

A previous study of exome-sequenced schizophrenia cases and controls reported an excess of singleton, gene-disruptive variants among cases, concentrated in particular gene sets. The dataset included a number of subjects with a substantial Finnish contribution to ancestry. We have reanalysed the same dataset after removal of these subjects and we have also included non-singleton variants of all types using a weighted burden test which assigns higher weights to variants predicted to have a greater effect on protein function. We investigated the same 31 gene sets as previously and also 1454 GO gene sets. The reduced dataset consisted of 4225 cases and 5834 controls. No individual variants or genes were significantly enriched in cases but 13 out of the 31 gene sets were significant after Bonferroni correction and the \"FMRP targets\" set produced a signed log p value (SLP) of 7.1. The gene within this set with the highest SLP, equal to 3.4, was FYN, which codes for a tyrosine kinase which phosphorylates glutamate metabotropic receptors and ionotropic NMDA receptors, thus modulating their trafficking, subcellular distribution and function. In the most recent GWAS of schizophrenia it was identified as a \"prioritized candidate gene\". Two of the subunits of the NMDA receptor which are substrates of FYN are coded for by GRIN1 (SLP=1.7) and GRIN2B (SLP=2.1). Of note, for some sets there was a substantial enrichment of non-singleton variants. Of 1454 GO gene sets, 3 were significant after Bonferroni correction. Identifying specific genes and variants will depend on genotyping them in larger samples and/or demonstrating that they cosegregate with illness within pedigrees.

genetics↗

bioRxiv2017

Biologics-associated Risks for Incident Skin and Soft Tissue Infections in Psoriasis Patients: Results from Propensity Score-Stratified Survival Analysis

BackgroundHow biologics affect psoriasis patients risks for SSTIs in a pragmatic clinical setting remains unclear.\n\nMethodsIn a cohort of adult psoriasis outpatients (aged 20 years or older) who visited the Dermatology Clinic in 2010-2015, we compared incident SSTI risks between patients using biologics (users) versus nonbiologics (nonusers). We also estimated SSTI risks in biologics-associated time-periods relative to nonbiologics only in users. We applied random effects Cox proportional hazard models with propensity score-stratification to account for differential baseline hazards.\n\nResultsOver a median follow-up of 2.8 years (interquartile range: 1.5, 4.3), 172 of 922 patients ever received biologics (18.7%); 233 SSTI incidents occurred during 2518.3 person-years, with an overall incidence of 9.3/100 person-years (95% confidence interval [CI]: 8.1, 10.6). In univariate analysis, users showed an 89% lower risk for SSTIs than nonusers (hazard ratio [HR]: 0.11, 95%CI: 0.05, 0.26); the association persisted in a multivariable model (adjusted HR: 0.26, 95%CI: 0.12, 0.58). Among biologics users, biologics-exposed time-periods were associated with a nonsignificant 21% increased risk (adjusted HR: 1.21, 95%CI: 0.41, 3.59).\n\nConclusionsDespite of adjusting for the underlying risk profiles, risk comparisons between biologics users and nonusers remained confounded by treatment selection. By comparing time-periods being exposed versus unexposed to biologics among users, the current analysis did not find evidence for an increased SSTI risk that was associated with biologics use in psoriasis patients.

epidemiology↗

bioRxiv2017

Mupirocin-associated temporal changes in the nasal microbiota and host’s antimicrobial responses: A pilot study in healthy staphylococcal carriers

BackgroundHow mupirocin affects the human nasal microbiota over time remains uncharacterized.\n\nMethodsWe repeatedly sampled the anterior nares of four healthy staphylococcal carriers before and after mupirocin use. By sequencing bacterial 16S ribosomal cDNA, we characterized sequential changes in the carriage status, the nasal microbiota, and the hosts antimicrobial peptide expression up to 90 days after decolonization.\n\nResultsBefore mupirocin use, the nasal microbiota differed by the initial, culture-based staphylococcal carriage status, with Firmicutes (54.1%) being the most predominant in carriers and Proteobacteria (75.8%) in the only noncarrier. The nasal microbiota became less diverse (Shannon diversity: 1.33, 95% confidence interval [CI]: 1.06-1.54) immediately after decolonisation than that before decolonisation (1.78, 95%CI: 0.58-1.93). Based on results of differential abundance analysis, Firmicutes were significantly enriched (log2 fold changes [≥] 4, Benjamini-Hochberg adjusted P < .01) while Actinobacteria, particularly Corynbebacterium, were relatively depleted in samples from staphylococcal carriers. Results of nonmetric multidimensional scaling (NMDS) and constrained correspondence analysis (CCA) also suggested that the initial staphylococcal carriage status, human neutrophil peptide 1 levels, and sampling times were major contributors to the between-community dissimilarities (P for marginal permutation test: .014) though the significance attenuated when within-group correlation was considered (P for blocked permutation test: .047).\n\nConclusionThese findings suggest that large-scale investigations on antibiotic effects on the human nasal microbiota are warranted.

microbiology↗