Biology subjects

Spector, T.

Publications and source records attributed to Spector, T..

2 recordsLinked to original sources

bioRxiv2018

Defining the genetic control of human blood plasma N-glycome using genome-wide association study

Glycosylation is a common post-translational modification of proteins. It is known, that glycans are directly involved in the pathophysiology of every major disease. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here, we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people. We discovered and replicated twelve loci. This allowed us to demonstrate a clear overlap in genetic control between total plasma and IgG glycosylation. Majority of loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3, and MGAT5). We, however, also found loci that are likely to reflect other, more complex, aspects of plasma glycosylation process. Functional genomic annotation suggested the role of DERL3, which potentially highlights the role of glycoprotein degradation pathway, and such transcription factor as IKZF1.

genetics↗

bioRxiv2016

Predicting causal variants affecting expression using whole genome sequence and RNA-seq from multiple human tissues.

Genetic association mapping produces statistical links between phenotypes and genomic regions, but identifying the causal variants themselves remains difficult. Complete knowledge of all genetic variants, as provided by whole genome sequence (WGS), will help, but is currently financially prohibitive for well powered GWAS studies. To explore the advantages of WGS in a well powered setting, we performed eQTL mapping using WGS and RNA-seq, and showed that the lead eQTL variants called using WGS are more likely to be causal. We derived properties of the causal variant from simulation studies, and used these to propose a method for implicating likely causal SNPs. This method predicts that 25% - 70% of the causal variants lie in open chromatin regions, depending on tissue and experiment. Finally, we identify a set of high confidence causal variants and show that they are more enriched in GWAS associations than other eQTL. Of these, we find 65 associations with GWAS traits and show examples where the gene implicated by expression has been functionally validated as relevant for complex traits.

genomics↗