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 language | English (US) |
|---|---|
| Pages (from-to) | 1958-1967 |
| Number of pages | 10 |
| Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Volume | 29 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2009 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin
AU - Paterson, Andrew D.
AU - Lopes-Virella, Maria F.
AU - Waggott, Daryl
AU - Boright, Andrew P.
AU - Hosseini, S. Mohsen
AU - Carter, Rickey E.
AU - Shen, Enqing
AU - Mirea, Lucia
AU - Bharaj, Bhupinder
AU - Sun, Lei
AU - Bull, Shelley B.
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - ABO blood group
KW - E-selectin
KW - Genome-wide association
KW - SNP
UR - http://www.scopus.com/inward/record.url?scp=73949157547&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73949157547&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.109.192971
DO - 10.1161/ATVBAHA.109.192971
M3 - Article
VL - 29
SP - 1958
EP - 1967
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 11
ER -