Heritability enrichment of immunoglobulin G N-glycosylation in specific tissues

Genome-wide association studies (GWAS) have identified over 60 genetic loci associated with immunoglobulin G (IgG) N-glycosylation; however, the causal genes and their abundance in relevant tissues are uncertain. Leveraging data from GWAS summary statistics for 8,090 Europeans, and large-scale expression quantitative trait loci (eQTL) data from the genotype-tissue expression of 53 types of tissues (GTEx v7), we derived a linkage disequilibrium score for the specific expression of genes (LDSC-SEG) and conducted a transcriptome-wide association study (TWAS). We identified 55 gene associations whose predicted levels of expression were significantly associated with IgG N-glycosylation in 14 tissues. Three working scenarios, i.e., tissue-specific, pleiotropic, and coassociated, were observed for candidate genetic predisposition affecting IgG N-glycosylation traits. Furthermore, pathway enrichment showed several IgG N-glycosylation-related pathways, such as asparagine N-linked glycosylation, N-glycan biosynthesis and transport to the Golgi and subsequent modification. Through phenome-wide association studies (PheWAS), most genetic variants underlying TWAS hits were found to be correlated with health measures (height, waist-hip ratio, systolic blood pressure) and diseases, such as systemic lupus erythematosus, inflammatory bowel disease, and Parkinson’s disease, which are related to IgG N-glycosylation. Our study provides an atlas of genetic regulatory loci and their target genes within functionally relevant tissues, for further studies on the mechanisms of IgG N-glycosylation and its related diseases

Differential Seroprevalence of Human Bocavirus Species 1-4 in Beijing, China

BACKGROUND: Four species of human bocaviruses (HBoV1-4) have been identified based on phylogenetic analysis since its first report in 2005. HBoV1 has been associated with respiratory disease, whereas HBoV2-4 are mainly detected in enteric infections. Although the prevalence of HBoVs in humans has been studied in some regions, it has not been well addressed globally. METHODOLOGY/PRINCIPAL FINDINGS: Cross-reactivity of anti-VP2 antibodies was detected between HBoV1, 2, 3, and 4 in mouse and human serum. The prevalence of specific anti-VP2 IgG antibodies against HBoV1-4 was determined in different age groups of healthy individuals aged 0-70 years old in Beijing, China, using a competition ELISA assay based on virus-like particles of HBoV1-4. The seroprevalence of HBoV1-4 was 50%, 36.9%, 28.7%, and 0.8%, respectively, in children aged 0-14 years (n = 244); whereas the seroprevalence of HBoV1-4 was 66.9%, 49.3%, 38.7% and 1.4%, respectively, in healthy adults (≥ 15 years old; n = 142). The seropositive rate of HBoV1 was higher than that of HBoV2, HBoV3, and HBoV4 in individuals older than 0.5 years. Furthermore, IgG seroconversion of HBoV1 (10/31, 32.3%), HBoV2 (8/31, 25.8%), and HBoV3 (2/31, 6.5%) was found in paired sera collected from children with respiratory tract infections who were positive for HBoV1 according to PCR analysis. CONCLUSIONS/SIGNIFICANCE: Our data indicate that HBoV1 is more prevalent than HBoV2, HBoV3, and HBoV4 in the population we sampled in Beijing, China, suggesting that HBoV species may play differential roles in disease