Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns
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 an...
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ftunivturku:oai:www.utupub.fi:10024/168964 2023-05-15T17:42:43+02:00 Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns Perola M. Salmi M. Sliz E. Kettunen J. Kalaoja M. Jokelainen J. Karhu T. Keinänen-Kiukaanniemi S. Järvelin M.-R. Herzig K.-H. Jalkanen S. Männikkö M. Salomaa V. Ahola-Olli A. Santalahti K. Raitakari O. Viinamäki H. Lehtimäki T. Sebert S. tyks, vsshp, tyks, vsshp MediCity, MediCity Research Laboratory sydäntutkimuskeskus, Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC) biolääketieteen laitos, yhteiset, Institute of Biomedicine 2607100 2607003 2607004 2022-10-28T14:02:10Z 616 607 https://www.utupub.fi/handle/10024/168964 https://jmg.bmj.com/content/56/9/607 en eng BMJ Publishing Group Britannia United Kingdom GB 56 10.1136/jmedgenet-2018-105965 Journal of Medical Genetics 9 https://www.utupub.fi/handle/10024/168964 https://jmg.bmj.com/content/56/9/607 URN:NBN:fi-fe2021042824787 0022-2593 2022 ftunivturku 2022-11-03T00:02:06Z 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. Other/Unknown Material Northern Finland University of Turku: UTUPub |
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University of Turku: UTUPub |
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ftunivturku |
language |
English |
description |
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. |
author2 |
tyks, vsshp, tyks, vsshp MediCity, MediCity Research Laboratory sydäntutkimuskeskus, Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC) biolääketieteen laitos, yhteiset, Institute of Biomedicine 2607100 2607003 2607004 |
author |
Perola M. Salmi M. Sliz E. Kettunen J. Kalaoja M. Jokelainen J. Karhu T. Keinänen-Kiukaanniemi S. Järvelin M.-R. Herzig K.-H. Jalkanen S. Männikkö M. Salomaa V. Ahola-Olli A. Santalahti K. Raitakari O. Viinamäki H. Lehtimäki T. Sebert S. |
spellingShingle |
Perola M. Salmi M. Sliz E. Kettunen J. Kalaoja M. Jokelainen J. Karhu T. Keinänen-Kiukaanniemi S. Järvelin M.-R. Herzig K.-H. Jalkanen S. Männikkö M. Salomaa V. Ahola-Olli A. Santalahti K. Raitakari O. Viinamäki H. Lehtimäki T. Sebert S. Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns |
author_facet |
Perola M. Salmi M. Sliz E. Kettunen J. Kalaoja M. Jokelainen J. Karhu T. Keinänen-Kiukaanniemi S. Järvelin M.-R. Herzig K.-H. Jalkanen S. Männikkö M. Salomaa V. Ahola-Olli A. Santalahti K. Raitakari O. Viinamäki H. Lehtimäki T. Sebert S. |
author_sort |
Perola M. |
title |
Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns |
title_short |
Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns |
title_full |
Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns |
title_fullStr |
Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns |
title_full_unstemmed |
Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns |
title_sort |
genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in finns |
publisher |
BMJ Publishing Group |
publishDate |
2022 |
url |
https://www.utupub.fi/handle/10024/168964 https://jmg.bmj.com/content/56/9/607 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_relation |
56 10.1136/jmedgenet-2018-105965 Journal of Medical Genetics 9 https://www.utupub.fi/handle/10024/168964 https://jmg.bmj.com/content/56/9/607 URN:NBN:fi-fe2021042824787 0022-2593 |
_version_ |
1766144628428374016 |