title: Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin.
abstract: BACKGROUND
  Elevated serum soluble E-selectin levels have been associated with a number of diseases. Although E-selectin levels are heritable, little is known about the specific genetic factors involved. E-selectin levels have been associated with the ABO blood group phenotype.
  
  
  RESULTS
  We performed a high-resolution genome-wide association study of serum soluble E-selectin levels in 685 white individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study to identify major loci influencing levels. Highly significant evidence for association (P=10(-29)) was observed for rs579459 near the ABO blood group gene, accounting for 19% of the variance in E-selectin levels. Levels of E-selectin were higher in O/O than O/A heterozygotes, which were likewise higher than A/A genotypes. Analysis of subgroups of A alleles reveals heterogeneity in the association, and even after this was accounted for, an intron 1 SNP remained significantly associated. We replicate the ABO association in nondiabetic individuals.
  
  
  CONCLUSIONS
  ABO is a major locus for serum soluble E-selectin levels. We excluded population stratification, fine-mapped the association to sub-A alleles, and also document association with additional variation in the ABO region.
authors.affiliation: Hospital for Sick Children, Toronto, Ontario, Canada. andrew.paterson@utoronto.ca
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
authors.forename: Daryl
authors.initials: D
authors.lastname: Waggott
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Boright
authors.forename: S Mohsen
authors.initials: SM
authors.lastname: Hosseini
authors.forename: Rickey E
authors.initials: RE
authors.lastname: Carter
authors.forename: Enqing
authors.initials: E
authors.lastname: Shen
authors.forename: Lucia
authors.initials: L
authors.lastname: Mirea
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Bharaj
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Bull
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics*; D019040:E-Selectin / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012995:Solubility
chemical_list: D000017:ABO Blood-Group System; D019040:E-Selectin