ArticleAmerican journal of human genetics2019
Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy.
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Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 48 citations in OpenAlex.
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- The genetic basis of autoimmunity seen through the lens of T cell functional traits.Nature communications · 2024Review
- Senescence-related genes and proteins in the development of Alzheimer's disease: evidence from transcriptomic and Mendelian randomization analysis.Frontiers in aging neuroscience · 2024Article
- Genetic relationship between the immune system and autism.Brain, behavior, & immunity - health · 2023Article
- Identifying genetic variants that influence the abundance of cell states in single-cell data.bioRxiv : the preprint server for biology · 2023Article
- Quality control and removal of technical variation of NMR metabolic biomarker data in ~120,000 UK Biobank participants.Scientific data · 2023Article
- Long Non-coding RNA ZFPM2-AS1: A Novel Biomarker in the Pathogenesis of Human Cancers.Molecular biotechnology · 2022Review
- Genetic Regulation of Cytokine Response in Patients with Acute Community-Acquired Pneumonia.Genes · 2022Article
- Genome-wide analyses of multiple obesity-related cytokines and hormones informs biology of cardiometabolic traits.Genome medicine · 2021Article
- Untangling the genetic link between type 1 and type 2 diabetes using functional genomics.Scientific reports · 2021Article
- Transcriptional profile of platelets and iPSC-derived megakaryocytes from whole-genome and RNA sequencing.Blood · 2021Article
- An expanded analysis framework for multivariate GWAS connects inflammatory biomarkers to functional variants and disease.European journal of human genetics : EJHG · 2021Article
- Multivariate Analysis and Modelling of multiple Brain endOphenotypes: Let's MAMBO!Computational and structural biotechnology journal · 2021Review
- Genetics meets proteomics: perspectives for large population-based studies.Nature reviews. Genetics · 2021Review
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Authors and funding
30 authors at 15 institutions in 4 countries.
Artika P NathCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, United Kingdom; Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: artika.nath@baker.edu.au.
Scott C RitchieCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, United Kingdom.
Nastasiya F GrinbergCambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, United Kingdom.
Howard Ho-Fung TangCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
Qin Qin HuangCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia; Department of Clinical Pathology, University of Melbourne, Parkville, Victoria 3010, Australia.
Shu Mei TeoCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, United Kingdom.
Ari V Ahola-OlliProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.
Peter WürtzResearch Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki 00014, Finland; Nightingale Health Ltd., Helsinki 00300, Finland.
Aki S HavulinnaInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland; National Institute of Health and Welfare, Helsinki 00271, Finland.
Kristiina SantalahtiMedicity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.
Niina PitkänenResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.
Mika KähönenFinnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland; Department of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland.
Leo-Pekka LyytikäinenDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.
Emma RaitoharjuDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.
Ilkka SeppäläDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.
Antti-Pekka SarinInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland; National Institute of Health and Welfare, Helsinki 00271, Finland.
Samuli RipattiInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland; Department of Public Health, University of Helsinki, Helsinki 00014, Finland; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Aarno PalotieInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Markus PerolaInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland; National Institute of Health and Welfare, Helsinki 00271, Finland.
Jorma S ViikariDepartment of Medicine, University of Turku, Turku 20520, Finland; Division of Medicine, Turku University Hospital, Turku 20520, Finland.
Sirpa JalkanenMedicity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.
Mikael MaksimowMedicity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.
Marko SalmiMedicity Research Laboratory and Institute of Biomedicine, University of Turku, Turku 20520, Finland.
Chris WallaceCambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, United Kingdom; MRC Biostatistics Unit, Institute of Public Health, Cambridge CB2 0SR, United Kingdom.
Olli T RaitakariResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland; The Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20520, Finland.
Veikko SalomaaMedicity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.
Gad AbrahamCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, United Kingdom; Department of Clinical Pathology, University of Melbourne, Parkville, Victoria 3010, Australia.
Johannes KettunenMedicity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland; Computational Medicine, Centre for Life Course Health Research, University of Oulu, Oulu 90014, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio 70211, Finland; Biocenter Oulu, University of Oulu, Oulu 90014, Finland.
Michael InouyeCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, United Kingdom; Department of Clinical Pathology, University of Melbourne, Parkville, Victoria 3010, Australia; The Alan Turing Institute, London, United Kingdom. Electronic address: mi336@medschl.cam.ac.uk.
University of Turku · FIUniversity of Cambridge · GBFimlab (Finland) · FIFinland University · FITampere University · FIUniversity of Melbourne · AUBaker Heart and Diabetes Institute · AUBroad Institute · USFinnish Institute for Health and Welfare · FIGenomics (United Kingdom) · GBHarvard University · USInstitute for Molecular Medicine Finland · FITampere University Hospital · FIUniversity of Eastern Finland · FIUniversity of Helsinki · FI
Funding
British Heart Foundation RG/13/13/30194British Heart Foundation RG/18/13/33946Medical Research Council MC_UU_00002/4Medical Research Council MR/L003120/1Wellcome TrustWellcome Trust WT107881
Abstract
Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain unknown. Here, we aimed to identify and characterize genetic variants with pleiotropic effects on cytokines. Using three population-based cohorts (n = 9,263), we performed multivariate genome-wide association studies (GWAS) for a correlation network of 11 circulating cytokines, then combined our results in meta-analysis. We identified a total of eight loci significantly associated with the cytokine network, of which two (PDGFRB and ABO) had not been detected previously. In addition, conditional analyses revealed a further four secondary signals at three known cytokine loci. Integration, through the use of Bayesian colocalization analysis, of publicly available GWAS summary statistics with the cytokine network associations revealed shared causal variants between the eight cytokine loci and other traits; in particular, cytokine network variants at the ABO, SERPINE2, and ZFPM2 loci showed pleiotropic effects on the production of immune-related proteins, on metabolic traits such as lipoprotein and lipid levels, on blood-cell-related traits such as platelet count, and on disease traits such as coronary artery disease and type 2 diabetes.
Indexed as
Genetic PleiotropyGenome-Wide Association StudyPolymorphism, Single NucleotideQuantitative Trait LociAdolescentAdultAgedBiomarkersBlood ProteinsCardiovascular DiseasesChildCytokinesFemaleFollow-Up StudiesGene Regulatory NetworksGenetic Predisposition to DiseaseBiomarkersBlood ProteinsCytokinesblood cell traitscardiometabolic diseasescolocalisation analysiscytokineseQTLsGWASmetabolitesmultivariate analysisprotein QTLs
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