Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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

View ORCID ProfileEeva Sliz, Marita Kalaoja, Ari Ahola-Olli, View ORCID ProfileOlli Raitakari, View ORCID ProfileMarkus Perola, View ORCID ProfileVeikko Salomaa, View ORCID ProfileTerho Lehtimäki, View ORCID ProfileToni Karhu, View ORCID ProfileHeimo Viinamäki, Marko Salmi, View ORCID ProfileKristiina Santalahti, View ORCID ProfileSirpa Jalkanen, Jari Jokelainen, View ORCID ProfileSirkka Keinänen-Kiukaanniemi, Minna Männikkö, View ORCID ProfileKarl-Heinz Herzig, Marjo-Riitta Järvelin, View ORCID ProfileSylvain Sebert, View ORCID ProfileJohannes Kettunen
doi: https://doi.org/10.1101/491852
Eeva Sliz
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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Eeva Sliz
Marita Kalaoja
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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ari Ahola-Olli
4Department of Internal Medicine, Satakunta Central Hospital, Pori, Finland.
5Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olli Raitakari
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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Olli Raitakari
Markus Perola
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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Markus Perola
Veikko Salomaa
7National Institute for Health and Welfare, Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Veikko Salomaa
Terho Lehtimäki
10Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Terho Lehtimäki
Toni Karhu
3Biocenter Oulu, Oulu, Finland
11Institute of Biomedicine, University of Oulu, Oulu, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Toni Karhu
Heimo Viinamäki
12Department of Psychiatry, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Heimo Viinamäki
Marko Salmi
13Medicity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kristiina Santalahti
13Medicity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kristiina Santalahti
Sirpa Jalkanen
13Medicity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sirpa Jalkanen
Jari Jokelainen
2Center for Life Course Health Research, University of Oulu, Oulu, Finland
14Unit of General Practice, Oulu University Hospital, Oulu, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sirkka Keinänen-Kiukaanniemi
2Center for Life Course Health Research, University of Oulu, Oulu, Finland
14Unit of General Practice, Oulu University Hospital, Oulu, Finland
15Oulu Deaconess Institute/Diapolis Oy Research Unit, Oulu, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sirkka Keinänen-Kiukaanniemi
Minna Männikkö
16Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karl-Heinz Herzig
3Biocenter Oulu, Oulu, Finland
11Institute of Biomedicine, 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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Karl-Heinz Herzig
Marjo-Riitta Järvelin
2Center for Life Course Health Research, University of Oulu, Oulu, Finland
3Biocenter Oulu, Oulu, Finland
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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sylvain Sebert
2Center for Life Course Health Research, University of Oulu, Oulu, Finland
3Biocenter Oulu, Oulu, Finland
21Department of Genomics and Complex Diseases, School of Public Health, Imperial College London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sylvain Sebert
  • For correspondence: johannes.kettunen@oulu.fi
Johannes Kettunen
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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Johannes Kettunen
  • For correspondence: johannes.kettunen@oulu.fi
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

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.

Methods To add understanding to the molecular mechanisms in inflammation, we performed a genome-wide association study (GWAS) on 16 circulating cytokines and cell adhesion molecules (inflammatory phenotypes) in Northern Finland Birth Cohort 1966 (NFBC1966, N=5,284). A subsequent meta-analysis was completed for 10 phenotypes available in a GWAS of three other Finnish population cohorts 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 confirmed six previously reported loci associating with at least one of the studied inflammatory phenotypes (p<3.1×10−9). We observed three loci associating with the concentration of soluble vascular cell adhesion molecule-1 (sVCAM-1), one of which is the ABO locus that has been previously associated with soluble E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) levels. Results from the complementary analyses suggest that the blood type B associates primarily with the concentration of sVCAM-1 while the A1 subtype shows a robust effect on sE-selectin and sICAM-1 levels. Furthermore, the genotypes in the ABO locus associating with higher soluble adhesion molecule levels tend to associate with lower low-density lipoprotein cholesterol level 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 at the ABO locus. The negative correlation between the genetic effects on soluble adhesion molecule levels and cardiovascular traits in this locus further suggests that increased soluble adhesion molecule levels per se may not be a risk factor for cardiovascular disease.

Abbreviations
GWAS
genome-wide association study
IL1α
interleukin 1-alpha
IL1β
interleukin 1-beta
IL1ra
interleukin 1 receptor antagonist
IL4
interleukin 4
IL6
interleukin 6
IL8
interleukin 8
IL17
interleukin 17
IP10
interferon gamma-induced protein 10
MAF
minor allele frequency
MCP1
monocyte chemoattractant protein 1
NFBC1966
Northern Finland Birth Cohort 1966
PAI-1
plasminogen activator inhibitor 1
sCD40L
soluble CD40 ligand
sE-selectin
soluble E-selectin
sICAM-1
soluble intercellular cell adhesion molecule 1
sVCAM-1
soluble vascular cell adhesion molecule 1
TNFα
tumor necrosis factor alpha
VEGF
vascular endothelial growth factor
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted December 10, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns
Eeva Sliz, Marita Kalaoja, Ari Ahola-Olli, Olli Raitakari, Markus Perola, Veikko Salomaa, Terho Lehtimäki, Toni Karhu, Heimo Viinamäki, Marko Salmi, Kristiina Santalahti, Sirpa Jalkanen, Jari Jokelainen, Sirkka Keinänen-Kiukaanniemi, Minna Männikkö, Karl-Heinz Herzig, Marjo-Riitta Järvelin, Sylvain Sebert, Johannes Kettunen
bioRxiv 491852; doi: https://doi.org/10.1101/491852
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns
Eeva Sliz, Marita Kalaoja, Ari Ahola-Olli, Olli Raitakari, Markus Perola, Veikko Salomaa, Terho Lehtimäki, Toni Karhu, Heimo Viinamäki, Marko Salmi, Kristiina Santalahti, Sirpa Jalkanen, Jari Jokelainen, Sirkka Keinänen-Kiukaanniemi, Minna Männikkö, Karl-Heinz Herzig, Marjo-Riitta Järvelin, Sylvain Sebert, Johannes Kettunen
bioRxiv 491852; doi: https://doi.org/10.1101/491852

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4085)
  • Biochemistry (8755)
  • Bioengineering (6477)
  • Bioinformatics (23331)
  • Biophysics (11740)
  • Cancer Biology (9144)
  • Cell Biology (13237)
  • Clinical Trials (138)
  • Developmental Biology (7410)
  • Ecology (11364)
  • Epidemiology (2066)
  • Evolutionary Biology (15084)
  • Genetics (10397)
  • Genomics (14006)
  • Immunology (9115)
  • Microbiology (22036)
  • Molecular Biology (8777)
  • Neuroscience (47345)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2480)
  • Physiology (3703)
  • Plant Biology (8045)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2207)
  • Systems Biology (6014)
  • Zoology (1249)