TY - JOUR
T1 - Genome-wide association study identifies two loci strongly affecting transferrin glycosylation
AU - Kutalik, Zoltán
AU - Benyamin, Beben
AU - Bergmann, Sven
AU - Mooser, Vincent
AU - Waeber, Gérard
AU - Montgomery, Grant W.
AU - Martin, Nicholas G.
AU - Madden, Pamela A.F.
AU - Heath, Andrew C.
AU - Beckmann, Jacques S.
AU - Vollenweider, Peter
AU - Marques-Vidal, Pedro
AU - Whitfield, John B.
N1 - Funding Information:
The CoLaus study was supported by research grants from GlaxoSmithKline. This work was supported by research grants from GlaxoSmithKline; Faculty of Biology and Medicine of Lausanne, Switzerland; Swiss National Science Foundation (33CSCO-122661); Australian National Health and Medical Research Council; EU 5th and 7th Framework Programmes (GenomEUtwin Project QLG2-CT-2002-01254); ENGAGE Consortium (HEALTH-F4-2007-201413) and U.S. National Institutes of Health (AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, DA12854, MH66206). Swiss National Science Foundation (33CSCO-122661 to S.B., 3100AO-116323/1 to S.B., 310000-112552 to J.S.B.); Giorgi-Cavaglieri Foundation to S.B.; Swiss Institute of Bioinformatics (Service Grant to S.B.); European Framework Project 6 (AnEuploidy and EuroDia projects to S.B.); National Health and Medical Research Council (NHMRC) Fellowships (552498, 339446 and 619667 to B.B. and G.W.M.).
PY - 2011/9
Y1 - 2011/9
N2 - 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 1 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.
AB - 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 1 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.
UR - https://www.scopus.com/pages/publications/80052225251
U2 - 10.1093/hmg/ddr272
DO - 10.1093/hmg/ddr272
M3 - Article
C2 - 21665994
AN - SCOPUS:80052225251
SN - 0964-6906
VL - 20
SP - 3710
EP - 3717
JO - Human molecular genetics
JF - Human molecular genetics
IS - 18
M1 - ddr272
ER -