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 and...
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ftimperialcol:oai:spiral.imperial.ac.uk:10044/1/85504 2023-05-15T17:42:55+02:00 Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns Sliz, E Kalaoja, M Ahola-Olli, A Raitakari, O Perola, M Salomaa, V Lehtimaki, T Karhu, T Viinamaki, H Salmi, M Santalahti, K Jalkanen, S Jokelainen, J Keinanen-Kiukaanniemi, S Mannikko, M Herzig, K-H Jarvelin, M-R Sebert, S Kettunen, J UNIVERSITY OF OULU 2019-04-20 http://hdl.handle.net/10044/1/85504 https://doi.org/10.1136/jmedgenet-2018-105965 English eng BMJ Publishing Group Journal of Medical Genetics 0022-2593 http://hdl.handle.net/10044/1/85504 doi:10.1136/jmedgenet-2018-105965 Nil © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. http://creativecommons.org/licenses/by-nc/4.0/ CC-BY-NC 616 607 Science & Technology Life Sciences & Biomedicine Genetics & Heredity E-SELECTIN INFLAMMATION DISEASE METAANALYSIS ACTIVATION EXPRESSION VCAM-1 RISK abo blood type genome-wide association inflammatory load svcam-1 Adult Cell Adhesion Molecules Cytokines Disease Susceptibility European Continental Ancestry Group Female Finland Genome-Wide Association Study Humans Inflammation Mediators Male Phenotype Polymorphism Single Nucleotide Quantitative Trait Loci 06 Biological Sciences 11 Medical and Health Sciences Journal Article 2019 ftimperialcol https://doi.org/10.1136/jmedgenet-2018-105965 2021-01-21T23:39:16Z 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. Article in Journal/Newspaper Northern Finland Imperial College London: Spiral Journal of Medical Genetics 56 9 607 616 |
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Open Polar |
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Imperial College London: Spiral |
op_collection_id |
ftimperialcol |
language |
English |
topic |
Science & Technology Life Sciences & Biomedicine Genetics & Heredity E-SELECTIN INFLAMMATION DISEASE METAANALYSIS ACTIVATION EXPRESSION VCAM-1 RISK abo blood type genome-wide association inflammatory load svcam-1 Adult Cell Adhesion Molecules Cytokines Disease Susceptibility European Continental Ancestry Group Female Finland Genome-Wide Association Study Humans Inflammation Mediators Male Phenotype Polymorphism Single Nucleotide Quantitative Trait Loci 06 Biological Sciences 11 Medical and Health Sciences |
spellingShingle |
Science & Technology Life Sciences & Biomedicine Genetics & Heredity E-SELECTIN INFLAMMATION DISEASE METAANALYSIS ACTIVATION EXPRESSION VCAM-1 RISK abo blood type genome-wide association inflammatory load svcam-1 Adult Cell Adhesion Molecules Cytokines Disease Susceptibility European Continental Ancestry Group Female Finland Genome-Wide Association Study Humans Inflammation Mediators Male Phenotype Polymorphism Single Nucleotide Quantitative Trait Loci 06 Biological Sciences 11 Medical and Health Sciences Sliz, E Kalaoja, M Ahola-Olli, A Raitakari, O Perola, M Salomaa, V Lehtimaki, T Karhu, T Viinamaki, H Salmi, M Santalahti, K Jalkanen, S Jokelainen, J Keinanen-Kiukaanniemi, S Mannikko, M Herzig, K-H Jarvelin, M-R Sebert, S Kettunen, J Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns |
topic_facet |
Science & Technology Life Sciences & Biomedicine Genetics & Heredity E-SELECTIN INFLAMMATION DISEASE METAANALYSIS ACTIVATION EXPRESSION VCAM-1 RISK abo blood type genome-wide association inflammatory load svcam-1 Adult Cell Adhesion Molecules Cytokines Disease Susceptibility European Continental Ancestry Group Female Finland Genome-Wide Association Study Humans Inflammation Mediators Male Phenotype Polymorphism Single Nucleotide Quantitative Trait Loci 06 Biological Sciences 11 Medical and Health Sciences |
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 |
UNIVERSITY OF OULU |
format |
Article in Journal/Newspaper |
author |
Sliz, E Kalaoja, M Ahola-Olli, A Raitakari, O Perola, M Salomaa, V Lehtimaki, T Karhu, T Viinamaki, H Salmi, M Santalahti, K Jalkanen, S Jokelainen, J Keinanen-Kiukaanniemi, S Mannikko, M Herzig, K-H Jarvelin, M-R Sebert, S Kettunen, J |
author_facet |
Sliz, E Kalaoja, M Ahola-Olli, A Raitakari, O Perola, M Salomaa, V Lehtimaki, T Karhu, T Viinamaki, H Salmi, M Santalahti, K Jalkanen, S Jokelainen, J Keinanen-Kiukaanniemi, S Mannikko, M Herzig, K-H Jarvelin, M-R Sebert, S Kettunen, J |
author_sort |
Sliz, E |
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 |
2019 |
url |
http://hdl.handle.net/10044/1/85504 https://doi.org/10.1136/jmedgenet-2018-105965 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
616 607 |
op_relation |
Journal of Medical Genetics 0022-2593 http://hdl.handle.net/10044/1/85504 doi:10.1136/jmedgenet-2018-105965 Nil |
op_rights |
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. http://creativecommons.org/licenses/by-nc/4.0/ |
op_rightsnorm |
CC-BY-NC |
op_doi |
https://doi.org/10.1136/jmedgenet-2018-105965 |
container_title |
Journal of Medical Genetics |
container_volume |
56 |
container_issue |
9 |
container_start_page |
607 |
op_container_end_page |
616 |
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1766144853815590912 |