title: Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors.
abstract: Circulating cytokines and growth factors are regulators of inflammation and have been implicated in autoimmune and metabolic diseases. In this genome-wide association study (GWAS) of up to 8,293 Finns we identified 27 genome-widely significant loci (p < 1.2 × 10-9) for one or more cytokines. Fifteen of the associated variants had expression quantitative trait loci in whole blood. We provide genetic instruments to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases. We further link inflammatory markers with variants previously associated with autoimmune diseases such as Crohn disease, multiple sclerosis, and ulcerative colitis and hereby elucidate the molecular mechanisms underpinning these diseases and suggest potential drug targets.
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520 Turku, Finland. Electronic address: avahol@utu.fi.
authors.forename: Ari V
authors.initials: AV
authors.lastname: Ahola-Olli
authors.affiliation: Computational Medicine, Center for Life Course Health Research, University of Oulu, 90014 Oulu, Finland.
authors.forename: Peter
authors.initials: P
authors.lastname: Würtz
authors.affiliation: National Institute of Health and Welfare, 00271 Helsinki, Finland.
authors.forename: Aki S
authors.initials: AS
authors.lastname: Havulinna
authors.affiliation: Medicity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, 20520 Turku, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aalto
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520 Turku, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Pitkänen
authors.affiliation: The Department of Clinical Chemistry, Fimlab Laboratories, Pirkanmaa Hospital District, School of Medicine, University of Tampere, 33014 Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: The Department of Clinical Physiology, Tampere University Hospital, 33521 Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: The Department of Clinical Chemistry, Fimlab Laboratories, Pirkanmaa Hospital District, School of Medicine, University of Tampere, 33014 Tampere, Finland.
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.affiliation: The Department of Clinical Chemistry, Fimlab Laboratories, Pirkanmaa Hospital District, School of Medicine, University of Tampere, 33014 Tampere, Finland.
authors.forename: Emma
authors.initials: E
authors.lastname: Raitoharju
authors.affiliation: The Department of Clinical Chemistry, Fimlab Laboratories, Pirkanmaa Hospital District, School of Medicine, University of Tampere, 33014 Tampere, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.affiliation: National Institute of Health and Welfare, 00271 Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Antti-Pekka
authors.initials: AP
authors.lastname: Sarin
authors.affiliation: National Institute of Health and Welfare, 00271 Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland; The Department of Public Health, University of Helsinki, 00271 Helsinki, Finland.
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Aarne
authors.initials: A
authors.lastname: Palotie
authors.affiliation: National Institute of Health and Welfare, 00271 Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: The Department of Medicine, University of Turku, 20520 Turku, Finland; Division of Medicine, Turku University Hospital, 20520 Turku, Finland.
authors.forename: Jorma S
authors.initials: JS
authors.lastname: Viikari
authors.affiliation: Medicity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, 20520 Turku, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: Medicity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, 20520 Turku, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Maksimow
authors.affiliation: National Institute of Health and Welfare, 00271 Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Medicity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, 20520 Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.affiliation: Computational Medicine, Center for Life Course Health Research, University of Oulu, 90014 Oulu, Finland; National Institute of Health and Welfare, 00271 Helsinki, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland; Biocenter Oulu, University of Oulu, 90014 Oulu, Finland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520 Turku, Finland; Biocenter Oulu, University of Oulu, 90014 Oulu, Finland; The Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20520 Turku, Finland.
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D016207:Cytokines / Q000097:blood*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007249:Inflammation / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins