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Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin.


ABSTRACT: 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.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.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.

SUBMITTER: Paterson AD 

PROVIDER: S-EPMC3147250 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin.

Paterson Andrew D AD   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  

Arteriosclerosis, thrombosis, and vascular biology 20090903 11


<h4>Background</h4>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.<h4>Methods and results</h4>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 T  ...[more]

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