University of Oulu

Sliz E, Kalaoja M, Ahola-Olli A, et al. Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns. Journal of Medical Genetics 2019;56:607-616.

Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns

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Author: Sliz, Eeva1,2,3; Kalaoja, Marita1,2,3; Ahola-Olli, Ari4,5;
Organizations: 1Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
2Center for Life Course Health Research, University of Oulu, Oulu, Finland
3Biocenter Oulu, Oulu, Finland
4Department of Internal Medicine, Satakunta Central Hospital, Pori, Finland
5Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
6Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
7National Institute for Health and Welfare, Helsinki, Finland
8Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
9University of Tartu, Estonian Genome Center, Tartu, Estonia
10Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
11Institute of Biomedicine, University of Oulu, Oulu, Finland
12Department of Psychiatry, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland
13Medicity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland
14Unit of General Practice, Oulu University Hospital, Oulu, Finland
15Oulu Deaconess Institute/Diapolis Oy Research Unit, Oulu, Finland
16Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland
17Medical Research Center (MRC), University of Oulu, and Oulu University Hospital, Oulu, Finland
18Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland
19Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK
20Unit of Primary Care, Oulu University Hospital, Oulu, Finland
21Department of Genomics and Complex Diseases, School of Public Health, Imperial College, London, UK
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021111755797
Language: English
Published: BMJ, 2019
Publish Date: 2021-11-23
Description:

Abstract

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.

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Series: Journal of medical genetics
ISSN: 0022-2593
ISSN-E: 1468-6244
ISSN-L: 0022-2593
Volume: 56
Issue: 9
Pages: 607 - 616
DOI: 10.1136/jmedgenet-2018-105965
OADOI: https://oadoi.org/10.1136/jmedgenet-2018-105965
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
1184 Genetics, developmental biology, physiology
Subjects:
Funding: This work was supported by the University of Oulu Graduate School (ES, MK), the Finnish Foundation for Cardiovascular Research (VS), Biocenter Oulu (SS), European Commission (DynaHEALTH – H2020 – 633595; SS), Academy of Finland (297338 and 307247; JK) and Novo Nordisk Foundation (NNF17OC0026062; JK). NFBC1966 received financial support from University of Oulu (Grant No 65354), Oulu University Hospital (Grant No 2/97 and 8/97), Ministry of Health and Social Affairs (Grant No 23/251/97, 160/97 and 190/97), National Institute for Health and Welfare, Helsinki (Grant No 54121), and Regional Institute of Occupational Health, Oulu, Finland (Grant No 50621 and 54231). The Young Finns Study has been financially supported by the Academy of Finland (grants 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi) and 41071 (Skidi)); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS); European Research Council (grant 742927 for MULTIEPIGEN project); and Tampere University Hospital Supporting Foundation.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
Academy of Finland Grant Number: 297338
307247
Detailed Information: 297338 (Academy of Finland Funding decision)
307247 (Academy of Finland Funding decision)
Copyright information: © 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/.
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