Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin.
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.
Paterson
Andrew D
AD
Hospital for Sick Children, Toronto, Ontario, Canada. andrew.paterson@utoronto.ca
Lopes-Virella
Maria F
MF
Waggott
Daryl
D
Boright
Andrew P
AP
Hosseini
S Mohsen
SM
Carter
Rickey E
RE
Shen
Enqing
E
Mirea
Lucia
L
Bharaj
Bhupinder
B
Sun
Lei
L
Bull
Shelley B
SB
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
D000017:ABO Blood-Group System; D019040:E-Selectin