RT Journal Article
SR Electronic
T1 Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 607
OP 616
DO 10.1136/jmedgenet-2018-105965
VO 56
IS 9
A1 Eeva Sliz
A1 Marita Kalaoja
A1 Ari Ahola-Olli
A1 Olli Raitakari
A1 Markus Perola
A1 Veikko Salomaa
A1 Terho Lehtimäki
A1 Toni Karhu
A1 Heimo Viinamäki
A1 Marko Salmi
A1 Kristiina Santalahti
A1 Sirpa Jalkanen
A1 Jari Jokelainen
A1 Sirkka Keinänen-Kiukaanniemi
A1 Minna Männikkö
A1 Karl-Heinz Herzig
A1 Marjo-Riitta Järvelin
A1 Sylvain Sebert
A1 Johannes Kettunen
YR 2019
UL http://jmg.bmj.com/content/56/9/607.abstract
AB Background Inflammatory processes contribute to the pathophysiology of multiple chronic conditions. Genetic factors play a crucial role in modulating the inflammatory load, but the exact mechanisms are incompletely understood.Objective To assess genetic determinants of 16 circulating cytokines and cell adhesion molecules (inflammatory phenotypes) in Finns.Methods Genome-wide associations of the inflammatory phenotypes were studied in Northern Finland Birth Cohort 1966 (N=5284). A subsequent meta-analysis was completed for 10 phenotypes available in a previous genome-wide association study, adding up to 13 577 individuals in the study. Complementary association tests were performed to study the effect of the ABO blood types on soluble adhesion molecule levels.Results We identified seven novel and six previously reported genetic associations (p<3.1×10−9). Three loci were associated with soluble vascular cell adhesion molecule-1 (sVCAM-1) level, one of which was the ABO locus that has been previously associated with soluble E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) levels. Our findings suggest that the blood type B associates primarily with sVCAM-1 level, while the A1 subtype shows a robust effect on sE-selectin and sICAM-1 levels. The genotypes in the ABO locus associating with higher soluble adhesion molecule levels tend to associate with lower circulating cholesterol levels and lower cardiovascular disease risk.Conclusion The present results extend the knowledge about genetic factors contributing to the inflammatory load. Our findings suggest that two distinct mechanisms contribute to the soluble adhesion molecule levels in the ABO locus and that elevated soluble adhesion molecule levels per se may not increase risk for cardiovascular disease.