Genome-wide association study identifies two loci strongly affecting transferrin glycosylation
Open Access
- 10 June 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 20 (18), 3710-3717
- https://doi.org/10.1093/hmg/ddr272
Abstract
Polysaccharide sidechains attached to proteins play important roles in cell–cell and receptor–ligand interactions. Variation in the carbohydrate component has been extensively studied for the iron transport protein transferrin, because serum levels of the transferrin isoforms asialotransferrin + disialotransferrin (carbohydrate-deficient transferrin, CDT) are used as biomarkers of excessive alcohol intake. We conducted a genome-wide association study to assess whether genetic factors affect CDT concentration in serum. CDT was measured in three population-based studies: one in Switzerland (CoLaus study, n = 5181) and two in Australia (n = 1509, n = 775). The first cohort was used as the discovery panel and the latter ones served as replication. Genome-wide single-nucleotide polymorphism (SNP) typing data were used to identify loci with significant associations with CDT as a percentage of total transferrin (CDT%). The top three SNPs in the discovery panel (rs2749097 near PGM1 on chromosome 1, and missense polymorphisms rs1049296, rs1799899 in TF on chromosome 3) were successfully replicated , yielding genome-wide significant combined association with CDT% (P = 1.9 × 10−9, 4 × 10−39, 5.5 × 10−43, respectively) and explain 5.8% of the variation in CDT%. These allelic effects are postulated to be caused by variation in availability of glucose-1-phosphate as a precursor of the glycan (PGM1), and variation in transferrin (TF) structure.This publication has 23 references indexed in Scilit:
- Common Variants in the Trichohyalin Gene Are Associated with Straight Hair in EuropeansAmerican Journal of Human Genetics, 2009
- Genotype ImputationAnnual Review of Genomics and Human Genetics, 2009
- Variants in TF and HFE Explain ∼40% of Genetic Variation in Serum-Transferrin LevelsAmerican Journal of Human Genetics, 2009
- Mapping the Genetic Architecture of Gene Expression in Human LiverPLoS Biology, 2008
- The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndromeBMC Cardiovascular Disorders, 2008
- WGAViewer: Software for genomic annotation of whole genome association studies: Figure 1.Genome Research, 2008
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- A new multipoint method for genome-wide association studies by imputation of genotypesNature Genetics, 2007
- Principal components analysis corrects for stratification in genome-wide association studiesNature Genetics, 2006
- Population Structure and EigenanalysisPLoS Genetics, 2006