Browsing by Author "Maja Barbalic"

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    Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
    (2018-11-01) Symen Ligthart; Ahmad Vaez; Urmo Võsa; Maria G. Stathopoulou; Paul S. de Vries; Bram P. Prins; Peter J. Van der Most; Toshiko Tanaka; Elnaz Naderi; Lynda M. Rose; Ying Wu; Robert Karlsson; Maja Barbalic; Honghuang Lin; René Pool; Gu Zhu; Aurélien Macé; Carlo Sidore; Stella Trompet; Massimo Mangino; Maria Sabater-Lleal; John P. Kemp; Ali Abbasi; Tim Kacprowski; Niek Verweij; Albert V. Smith; Tao Huang; Carola Marzi; Mary F. Feitosa; Kurt K. Lohman; Marcus E. Kleber; Yuri Milaneschi; Christian Mueller; Mahmudul Huq; Efthymia Vlachopoulou; Leo Pekka Lyytikäinen; Christopher Oldmeadow; Joris Deelen; Markus Perola; Jing Hua Zhao; Bjarke Feenstra; Behrooz Z. Alizadeh; H. Marike Boezen; Lude Franke; Pim van der Harst; Gerjan Navis; Marianne Rots; Harold Snieder; Morris Swertz; Bruce H.R. Wolffenbuttel; Cisca Wijmenga; Marzyeh Amini; Emelia Benjamin; Daniel I. Chasman; Abbas Dehghan; Tarunveer Singh Ahluwalia; James Meigs; Russell Tracy; Josh Bis; Gudny Eiriksdottir; Nathan Pankratz; Myron Gross; Alex Rainer; James G. Wilson; Bruce M. Psaty; Josee Dupuis; Bram Prins; Urmo Vaso; Maria Stathopoulou; Terho Lehtimaki; Wolfgang Koenig; Yalda Jamshidi; Sophie Siest; Andre G. Uitterlinden; Mohammadreza Abdollahi; Renate Schnabel; Ursula M. Schick; Ilja M. Nolte; Aldi Kraja; Yi Hsiang Hsu; Daniel S. Tylee; Alyson Zwicker; Rudolf Uher; George Davey-Smith; Alanna C. Morrison; Andrew Hicks; Cornelia M. van Duijn; Cavin Ward-Caviness; Eric Boerwinkle; J. Rotter; Ken Rice; Leslie Lange; Markus Perola; Eco de Geus; Andrew P. Morris; Amsterdam Public Health; Fimlab Laboratoriot Oy; Deutsches Zentrum für Herz-Kreislauf-Forschung e. V.; National Institute for Health and Welfare; Institut dInvestigació Biomèdica Sant Pau (IIB Sant Pau); Université de Lorraine; Max Planck Institute for Biology of Ageing; Hunter Medical Research Institute, Australia; Icelandic Heart Association; Haskoli Islands; University of Tartu; Harvard School of Public Health; Erasmus University Medical Center; University of Cambridge; University of Queensland; Swiss Institute of Bioinformatics; Wake Forest University Health Sciences; University of Cambridge, School of Clinical Medicine; Statens Serum Institut; The University of North Carolina at Chapel Hill; QIMR Berghofer Medical Research Institute; Helmholtz Center Munich German Research Center for Environmental Health; Washington University School of Medicine in St. Louis; Institut Universitaire de Médecine Sociale et Préventive Lausanne; Ernst-Moritz-Arndt-Universität Greifswald; Consiglio Nazionale delle Ricerche; Isfahan University of Medical Sciences; National Institute on Aging; University of Newcastle, Faculty of Health and Medicine; Brigham and Women's Hospital; Leiden University Medical Center - LUMC; Universitätsklinikum Schleswig-Holstein Campus Lübeck; Peking University; University of Bristol, Faculty of Medicine and Dentistry; University of Texas School of Public Health; Karolinska Institutet; King's College London; Tampereen Yliopisto; Vrije Universiteit Amsterdam; Sveučilište u Splitu; Boston University School of Medicine; University of Groningen, University Medical Center Groningen; Guy's and St Thomas' NHS Foundation Trust; Wellcome Sanger Institute; Universitätsklinikum Hamburg-Eppendorf und Medizinische Fakultät; Helsingin Yliopisto; Universitätsklinikum Mannheim; Université de Lausanne (UNIL); German Center for Diabetes Research (DZD); German Center for Cardiovascular Research, Partner Site RheinMain
    © 2018 American Society of Human Genetics C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10−8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.