The impact of immunoglobulin G N-glycosylation level on COVID-19 outcome: evidence from a Mendelian randomization study

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID‐19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran’s Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results.ResultsWe found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92–0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy.ConclusionsOur study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels

A comprehensive genome-wide cross-trait analysis of sexual factors and uterine leiomyoma.

Age at first sexual intercourse (AFS) and lifetime number of sexual partners (NSP) may influence the pathogenesis of uterine leiomyoma (UL) through their associations with hormonal concentrations and uterine infections. Leveraging summary statistics from large-scale genome-wide association studies conducted in European ancestry for each trait (NAFS = 214,547; NNSP = 370,711; NUL = 302,979), we observed a significant negative genomic correlation for UL with AFS (rg = -0.11, P = 7.83×10-4), but not with NSP (rg = 0.01, P = 0.62). Four specific genomic regions were identified as contributing significant local genetic correlations to AFS and UL, including one genomic region further identified for NSP and UL. Partitioning SNP-heritability with cell-type-specific annotations, a close clustering of UL with both AFS and NSP was identified in immune and blood-related components. Cross-trait meta-analysis revealed 15 loci shared between AFS/NSP and UL, including 7 novel SNPs. Univariable two-sample Mendelian randomization (MR) analysis suggested no evidence for a causal association between genetically predicted AFS/NSP and risk of UL, nor vice versa. Multivariable MR adjusting for age at menarche or/and age at natural menopause revealed a significant causal effect of genetically predicted higher AFS on a lower risk of UL. Such effect attenuated to null when age at first birth was further included. Utilizing participant-level data from the UK Biobank, one-sample MR based on genetic risk scores yielded consistent null findings among both pre-menopausal and post-menopausal females. From a genetic perspective, our study demonstrates an intrinsic link underlying sexual factors (AFS and NSP) and UL, highlighting shared biological mechanisms rather than direct causal effects. Future studies are needed to elucidate the specific mechanisms involved in the shared genetic influences and their potential impact on UL development

A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers

Summary: Little is known regarding the long-term adverse effects of COVID-19 on female-specific cancers, nor the shared genetic influences underlying these conditions. We performed a comprehensive genome-wide cross-trait analysis to investigate the shared genetic architecture between COVID-19 (infection, hospitalization, and critical illness) with three female-specific cancers (breast cancer (BC), epithelial ovarian cancer (EOC), and endometrial cancer (EC)). We identified significant genome-wide genetic correlations with EC for both hospitalization (rg = 0.19, p = 0.01) and critical illness (rg = 0.29, p = 3.00 × 10−4). Mendelian randomization demonstrated no valid association of COVID-19 with any cancer of interest, except for suggestive associations of genetically predicted hospitalization (ORIVW = 1.09, p = 0.04) and critical illness (ORIVW = 1.06, p = 0.04) with EC risk, none withstanding multiple correction. Cross-trait meta-analysis identified 20 SNPs shared between COVID-19 with BC, 15 with EOC, and 5 with EC; and transcriptome-wide association studies revealed multiple shared genes. Findings support intrinsic links underlying these complex traits, highlighting shared mechanisms rather than causal associations

A cocrystallized catalyst-coated membrane with high performance for solid polymer electrolyte water electrolysis

A cocrystallized catalyst-coated membrane (CCM) is prepared by together heating amorphous Nafion membrane and catalyst layers at 120 degrees C to develop the membrane electrode assembly for solid polymer electrolyte (SPE) water electrolysis. The cocrystallization treatment effectively reinforces the bonding between membrane and catalyst layers, and increases the hydrophobicity of the catalyst layers. The SPE water electrolyser with the cocrystallized CCM decreased cell voltage by 0.09 V at 2000 mA cm(-2) at 80 degrees C and improved the stability in comparison with the conventional CCM. (C) 2013 Elsevier B.V. All rights reserved

Preparation and characterization of partial-cocrystallized catalyst-coated membrane for solid polymer electrolyte water electrolysis

A novel catalyst-coated membrane (CCM) for solid polymer electrolyte water electrolysis was fabricated by together crystallizing partial-crystallized Nafion membrane and catalyst layers. The properties and performance of the partial-cocrystallized CCM (PCCCM) were evaluated and analyzed by destructive soaking test, scanning electron microscope, mercury intrusion and single cell test. The results revealed that the optimum annealing temperature and time for fabricating partial-crystallized Nafion membrane and PCCCM was 100 degrees C for 4 h and 120 degrees C for 4 h, respectively. The PCCCM not only possessed much stronger cohesion between membrane and catalyst layers, but also had higher porosity than conventional CCM. The electrolysis Voltage of the SPE water electrolyser with the new CCM was as low as 1.748 V at 2000 mA cm(-2) under 80 degrees C and atmospheric pressure: Moreover, there was no obvious increase of electrolysis voltage during stability test conducted under 2000 mA cm(-2) for about 180 h. Copyright (C) 2013, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved

Local genetic correlations between uterine leiomyoma and sexual factors.

(A). Manhattan plot presenting region-specific P-values for local genetic correlation between uterine leiomyoma and age at first sexual intercourse. (B). Manhattan plot presenting region-specific P-values for local genetic correlation between uterine leiomyoma and lifetime number of sexual partners. Red dots represent loci showing significant local genetic correlation after multiple testing adjustment (P < 0.05/2,353). AFS, age at first sexual intercourse; UL, uterine leiomyoma; NSP, lifetime number of sexual partners.</p

Results from local genetic correlation analysis conducted for age at first sexual intercourse and uterine leiomyoma.

Results from local genetic correlation analysis conducted for age at first sexual intercourse and uterine leiomyoma.</p

Supplementary methods for mediation analysis and an interpretation and discussion of the mediation analysis results.

Supplementary methods for mediation analysis and an interpretation and discussion of the mediation analysis results.</p

Characteristics of genetic instruments identified by GWAS to be associated with lifetime number of sexual partners.

Characteristics of genetic instruments identified by GWAS to be associated with lifetime number of sexual partners.</p

Overall study design of genome-wide cross-trait analysis.

GWAS summary statistics for each trait of interest were retrieved from publicly available GWAS(s). A global genetic correlation analysis between sexual factors and uterine leiomyoma was conducted. The estimated global genetic correlation was further dissected at LD-defined regions. Functional annotation analysis within 396 cell-type-specific annotations was conducted on three traits by using genome-wide SNPs. Cross-trait meta-analysis was applied to identify pleiotropic loci, and a comprehensive Mendelian randomization analysis was used to infer putative causal relationships.</p