@article{ab927a49d7f148fba141b28e3f06560a,
title = "Genetic variants in ABO blood group region, plasma soluble E-selectin levels and risk of type 2 diabetes",
abstract = "Blood soluble E-selectin (sE-selectin) levels have been related to various conditions such as type 2 diabetes. We performed a genome-wide association study among women of European ancestry from the Nurses' Health Study, and identified genome-wide significant associations between a cluster of markers at the ABO locus (9q34) and plasma sE-selectin concentration. The strongest association was with rs651007, which explained ~9.71% of the variation in sE-selectin concentrations. SNP rs651007 was also nominally associated with soluble intracellular cell adhesion molecule-1 (sICAM-1) (P = 0.026) and TNF-R2 levels (P = 0.018), independent of sE-selectin. In addition, the genetic-inferred ABO blood group genotypes were associated with sE-selectin concentrations (P = 3.55 3 10-47). Moreover, we found that the genetic-inferred blood group B was associated with a decreased risk (OR = 0.44, 0.27-0.70) of type 2 diabetes compared with blood group O, adjusting for sE-selectin, sICAM-1, TNF-R2 and other covariates. Our findings indicate that the genetic variants at ABO locus affect plasma sE-selectin levels and diabetes risk. The genetic associations with diabetes risk were independent of sE-selectin levels.",
author = "Lu Qi and Cornelis, {Marilyn C.} and Peter Kraft and Majken Jensen and {van Dam}, {Rob M.} and Qi Sun and Girman, {Cynthia J.} and Laurie, {Cathy C.} and Mirel, {Daniel B.} and Hunter, {David J.} and Eric Rimm and Hu, {Frank B.}",
note = "Funding Information: The NHS type 2 diabetes GWA study (U01HG004399) is a component of a collaborative project that includes 13 other GWA studies (U01HG004738, U01HG004422, U01HG004 402, U01HG004729, U01HG004726, U01HG004735, U01H G004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033; National Institute of Dental & Craniofacial Research: U01DE018993, U01DE018903) funded as part of the Gene Environment-Association Studies (GENEVA) under the NIH Genes, Environment and Health Initiative (GEI). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Genotyping was performed at the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and the NIH contract {\textquoteleft}High throughput genotyping for studying the genetic contributions to human disease{\textquoteright} (HHSN268200782096C). Additional funding for the current research was provided by the National Cancer Institute (P01CA087969, P01CA055075), the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845) and Merck & Co., Inc. L.Q. is supported by National Institutes of Health grants RO1 HL71981, American Heart Association Scientist Development Award and the Boston Obesity Nutrition Research Center (DK46200). M.C. Cornelis is a recipient of a Canadian Institutes of Health Research Fellowship.",
year = "2010",
month = feb,
day = "10",
doi = "10.1093/hmg/ddq057",
language = "English (US)",
volume = "19",
pages = "1856--1862",
journal = "Human molecular genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "9",
}
