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

Andrew D. Paterson, Maria F. Lopes-Virella, Daryl Waggott, Andrew P. Boright, S. Mohsen Hosseini, Rickey E. Carter, Enqing Shen, Lucia Mirea, Bhupinder Bharaj, Lei Sun, Shelley B. Bull

Research output: Contribution to journalArticle

110 Citations (Scopus)

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. METHODS AND 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) 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. CONCLUSION-: 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.

Original languageEnglish (US)
Pages (from-to)1958-1967
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume29
Issue number11
DOIs
StatePublished - Nov 2009
Externally publishedYes

Fingerprint

E-Selectin
Blood Group Antigens
Genome
Serum
Diabetes Complications
Alleles
Genome-Wide Association Study
Heterozygote
Type 1 Diabetes Mellitus
Introns
Single Nucleotide Polymorphism
Epidemiology
Genotype
Phenotype
Population
Genes

Keywords

  • ABO blood group
  • E-selectin
  • Genome-wide association
  • SNP

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin. / Paterson, Andrew D.; Lopes-Virella, Maria F.; Waggott, Daryl; Boright, Andrew P.; Hosseini, S. Mohsen; Carter, Rickey E.; Shen, Enqing; Mirea, Lucia; Bharaj, Bhupinder; Sun, Lei; Bull, Shelley B.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 29, No. 11, 11.2009, p. 1958-1967.

Research output: Contribution to journalArticle

Paterson, AD, Lopes-Virella, MF, Waggott, D, Boright, AP, Hosseini, SM, Carter, RE, Shen, E, Mirea, L, Bharaj, B, Sun, L & Bull, SB 2009, 'Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 11, pp. 1958-1967. https://doi.org/10.1161/ATVBAHA.109.192971
Paterson, Andrew D. ; Lopes-Virella, Maria F. ; Waggott, Daryl ; Boright, Andrew P. ; Hosseini, S. Mohsen ; Carter, Rickey E. ; Shen, Enqing ; Mirea, Lucia ; Bharaj, Bhupinder ; Sun, Lei ; Bull, Shelley B. / Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2009 ; Vol. 29, No. 11. pp. 1958-1967.
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