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J Med Genet. 2019 Jun 19. pii: jmedgenet-2018-105965. doi: 10.1136/jmedgenet-2018-105965. [Epub ahead of print]

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

Author information

1
Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland.
2
Center for Life Course Health Research, University of Oulu, Oulu, Finland.
3
Biocenter Oulu, Oulu, Finland.
4
Department of Internal Medicine, Satakunta Central Hospital, Pori, Finland.
5
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
6
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
7
National Institute for Health and Welfare, Helsinki, Finland.
8
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
9
University of Tartu, Estonian Genome Center, Tartu, Estonia.
10
Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
11
Institute of Biomedicine, University of Oulu, Oulu, Finland.
12
Department of Psychiatry, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
13
Medicity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland.
14
Unit of General Practice, Oulu University Hospital, Oulu, Finland.
15
Oulu Deaconess Institute/Diapolis Oy Research Unit, Oulu, Finland.
16
Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland.
17
Medical Research Center (MRC), University of Oulu, and Oulu University Hospital, Oulu, Finland.
18
Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland.
19
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
20
Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
21
Department of Genomics and Complex Diseases, School of Public Health, Imperial College, London, UK.
22
Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland johannes.kettunen@oulu.fi.
#
Contributed equally

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.

KEYWORDS:

abo blood type; genome-wide association; inflammatory load; svcam-1

PMID:
31217265
DOI:
10.1136/jmedgenet-2018-105965
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Conflict of interest statement

Competing interests: VS has participated in a conference trip sponsored by Novo Nordisk and received a honorarium from the same source for participating in and advisory board meeting. He also has ongoing research collaboration with Bayer.

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