Journal article

Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy

Artika P Nath, Scott C Ritchie, Nastasiya F Grinberg, Howard Ho-Fung Tang, Qin Qin Huang, Shu Mei Teo, Ari V Ahola-Olli, Peter Wurtz, Aki S Havulinna, Kristiina Santalahti, Niina Pitkanen, Terho Lehtimaki, Mika Kahonen, Leo-Pekka Lyytikainen, Emma Raitoharju, Ilkka Seppala, Antti-Pekka Sarin, Samuli Ripatti, Aarno Palotie, Markus Perola Show all

The American Journal of Human Genetics | CELL PRESS | Published : 2019

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 associa..

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Grants

Awarded by UK Medical Research Council


Awarded by British Heart Foundation


Awarded by Academy of Finland


Awarded by Competitive State Research Financing of the Expert Responsibility area of Kuopio University Hospital


Awarded by Competitive State Research Financing of the Expert Responsibility area of Turku University Hospital


Awarded by EU Horizon 2020


Awarded by ERC


Awarded by NHMRC Early Career Fellowship


Awarded by Wellcome Trust


Awarded by Medical Research Council


Awarded by Novo Nordisk Foundation


Awarded by Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital


Funding Acknowledgements

This work was supported partially by the Victorian Government's OIS Program and by core funding from: the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194, RG/18/13/33946), and the NIHR (Cambridge BRC at the Cambridge University Hospitals NHS Foundation Trust). The YFS was supported by the Academy of Finland: 322098, 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 (X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjo Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (755320-TAXINOMISIS); ERC (742927-MULTIEPIGEN project); and Tampere University Hospital Supporting Foundation. The views expressed are those of the authors and not necessarily those of the NHS, NIHR, or DHSC. The authors acknowledge support from: A.P.N., Australian Postgraduate Award; M.I. and S.C.R., NIHR (Cambridge BRC at the Cambridge University Hospitals NHS Foundation Trust); G.A., NHMRC Early Career Fellowship (1090462); Q.Q.H., Melbourne Research Scholarship; H.H.T., NHMRC Postgraduate Scholarship; N.F.G. and C.W., Wellcome Trust (WT107881); C.W., Medical Research Council (MC_UU_00002/4); J.K., Sigrid Juselius Foundation, Academy of Finland (297338 and 307247) and Novo Nordisk Foundation (NNF17OC0026062); P.W., Novo Nordisk Foundation (15998) and Academy of Finland (312476 and 312477); T.L., Academy of Finland (322098); A.S.H., Academy of Finland (321356); and V.S., Finnish Foundation for Cardiovascular Research.