%0 Journal Article
%T Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
%A A.W. Musk
%A Abbas Dehghan
%A Ahmad Vaez
%A Alan L. James
%A Alan R. Shuldiner
%A Alanna C. Morrison
%A Albert Hofman
%A Albert V. Smith
%A Albertine J. Oldehinkel
%A Alex P. Reiner
%A Alexander Teumer
%A Ali Abbasi
%A Anders Hamsten
%A Anders Larsson
%A Andrew A. Hicks
%A Andrew C. Heath
%A Andrew P. Morris
%A Andr¨¦ G. Uitterlinden
%A Annette Peters
%A Anton J.M. de Craen
%A Antonietta Robino
%A Anubha Mahajan
%A Aur¨¦lien Mac¨¦
%A Ayse Bilge Ozel
%A Beate St. Pourcain
%A Benjamin Lehne
%A Beverly Balkau
%A Bhoom Suktitipat
%A Bjarke Feenstra
%A Bradford B. Worrall
%A Bram P. Prins
%A Brenda W.J.H. Penninx
%A Brendan M. Buckley
%A Bruce M. Psaty
%A CHARGE Inflammation Working Group
%A Carla M.T. Tiesler
%A Carlo Sidore
%A Carlos F. Mendes de Leon
%A Carola Marzi
%A Caroline Hayward
%A Catharina A. Hartman
%A Cecilia M. Lindgren
%A Charles Kooperberg
%A Christian Fuchsberger
%A Christian Mueller
%A Christie M. Ballantyne
%A Christopher Oldmeadow
%A Claes Ohlsson
%A Claudia Langenberg
%A Claudia Schurmann
%A Craig E. Pennell
%A Cristina Bombieri
%A Cristina Menni
%A Dan Mellstr£¿m
%A Daniel I. Chasman
%A Daniela Ruggiero
%A David J. Stott
%A David Liewald
%A David M. Evans
%A David P. Strachan
%A Dena Hernandez
%A Denis A. Evans
%A Dhananjay Vaidya
%A Diana van Heemst
%A Diane M. Becker
%A Diego Vozzi
%A Donna K. Arnett
%A Dorret I. Boomsma
%A Dragana Vuckovic
%A Eco J.C.N. de Geus
%A Edith Hofer
%A Eero Kajantie
%A Efthymia Vlachopoulou
%A Elisabeth Thiering
%A Elisabetta Trabetti
%A Elizabeth G. Holliday
%A Elnaz Naderi
%A Emelia J. Benjamin
%A Eric Boerwinkle
%A Erik Ingelsson
%A Erin N. Smith
%A Erwin P. Bottinger
%A Evelin Mihailov
%A Fabiola Del Greco M.
%A Fernando Rivadineira
%A Francesco Cucca
%A Franco Giulianini
%J Archive of "American Journal of Human Genetics".
%D 2018
%R 10.1016/j.ajhg.2018.09.009
%X 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 ¡Á 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
%K C-reactive protein
%K genome-wide association study
%K inflammation
%K Mendelian randomization
%K inflammatory disorders
%K DEPICT
%K coronary artery disease
%K schizophrenia
%K system biology
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218410/