Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.

Am J Hum Genet
Publication type
Journal Article
Authors
Symen Ligthart
Ahmad Vaez
Urmo Võsa
Maria Stathopoulou
Paul de Vries
Bram Prins
Peter van der Most
Toshiko Tanaka
Elnaz Naderi
Lynda Rose
Ying Wu
Robert Karlsson
Maja Barbalic
Honghuang Lin
René Pool
Gu Zhu
Aurelien Macé
Carlo Sidore
Stella Trompet
Massimo Mangino
Maria Sabater-Lleal
John Kemp
Ali Abbasi
Tim Kacprowski
Niek Verweij
Albert Smith
Tao Huang
Carola Marzi
Mary Feitosa
Kurt Lohman
Marcus Kleber
Yuri Milaneschi
Christian Mueller
Mahmudul Huq
Efthymia Vlachopoulou
Leo-Pekka Lyytikäinen
Christopher Oldmeadow
Joris Deelen
Markus Perola
Jing Zhao
Bjarke Feenstra
LifeLines Cohort Study
Marzyeh Amini
CHARGE inflammation working group
Jari Lahti
Katharina Schraut
Myriam Fornage
Bhoom Suktitipat
Wei-Min Chen
Xiaohui Li
Teresa Nutile
Giovanni Malerba
Jian'an Luan
Tom Bak
Nicholas Schork
Fabiola M
Elisabeth Thiering
Anubha Mahajan
Riccardo Marioni
Evelin Mihailov
Joel Eriksson
Ayse Ozel
Weihua Zhang
Maria Nethander
Yu-Ching Cheng
Stella Aslibekyan
Wei Ang
Ilaria Gandin
Loic Yengo
Laura Portas
Charles Kooperberg
Edith Hofer
Kumar Rajan
Claudia Schurmann
Wouter Hollander
Tarunveer Ahluwalia
Jing Zhao
Harmen Draisma
Ian Ford
Nicholas Timpson
Alexander Teumer
Hongyan Huang
Simone Wahl
Yongmei Liu
Jie Huang
Hae-Won Uh
Frank Geller
Peter Joshi
Lisa Yanek
Elisabetta Trabetti
Benjamin Lehne
Diego Vozzi
Marie Verbanck
Ginevra Biino
Yasaman Saba
Ingrid Meulenbelt
Jeff O'Connell
Markku Laakso
Franco Giulianini
Patrik Magnusson
Christie Ballantyne
Jouke Hottenga
Grant Montgomery
Fernando Rivadineira
Rico Rueedi
Maristella Steri
Karl-Heinz Herzig
David Stott
Cristina Menni
Mattias Frånberg
Beate St Pourcain
Stephan Felix
Tune Pers
Stephan Bakker
Peter Kraft
Annette Peters
Dhananjay Vaidya
Graciela Delgado
Johannes Smit
Vera Großmann
Juha Sinisalo
Ilkka Seppälä
Stephen Williams
Elizabeth Holliday
Matthijs Moed
Claudia Langenberg
Katri Räikkönen
Jingzhong Ding
Harry Campbell
Michèle Sale
Yii-Der Chen
Alan James
Daniela Ruggiero
Nicole Soranzo
Catharina Hartman
Erin Smith
Gerald Berenson
Christian Fuchsberger
Dena Hernandez
Carla Tiesler
Vilmantas Giedraitis
David Liewald
Krista Fischer
Dan Mellström
Anders Larsson
Yunmei Wang
William Scott
Matthias Lorentzon
John Beilby
Kathleen Ryan
Craig Pennell
Dragana Vuckovic
Beverly Balkau
Maria Concas
Reinhold Schmidt
Carlos de Leon
Erwin Bottinger
Margreet Kloppenburg
Lavinia Paternoster
Michael Boehnke
A Musk
Gonneke Willemsen
David Evans
Pamela Madden
Mika Kähönen
Zoltán Kutalik
Magdalena Zoledziewska
Ville Karhunen
Stephen Kritchevsky
Naveed Sattar
Genevieve Lachance
Robert Clarke
Tamara Harris
Olli Raitakari
John Attia
Diana van Heemst
Eero Kajantie
Rossella Sorice
Giovanni Gambaro
Robert Scott
Andrew Hicks
Luigi Ferrucci
Marie Standl
Cecilia Lindgren
John Starr
Magnus Karlsson
Lars Lind
Jun Li
John Chambers
Trevor Mori
Eco de Geus
Andrew Heath
Nicholas Martin
Juha Auvinen
Brendan Buckley
Anton de Craen
Melanie Waldenberger
Konstantin Strauch
Thomas Meitinger
Rodney Scott
Mark McEvoy
Marian Beekman
Cristina Bombieri
Paul Ridker
Karen Mohlke
Nancy Pedersen
Alanna Morrison
Dorret Boomsma
John Whitfield
David Strachan
Albert Hofman
Peter Vollenweider
Francesco Cucca
Marjo-Riitta Jarvelin
J Wouter Jukema
Tim Spector
Anders Hamsten
Tanja Zeller
André Uitterlinden
Matthias Nauck
Vilmundur Gudnason
Lu Qi
Harald Grallert
Ingrid Borecki
Jerome Rotter
Winfried März
Philipp Wild
Marja-Liisa Lokki
Michael Boyle
Veikko Salomaa
Mads Melbye
Johan Eriksson
James Wilson
Brenda Penninx
Diane Becker
Bradford Worrall
Greg Gibson
Ronald Krauss
Marina Ciullo
Gianluigi Zaza
Nicholas Wareham
Albertine Oldehinkel
Lyle Palmer
Sarah Murray
Peter Pramstaller
Stefania Bandinelli
Joachim Heinrich
Erik Ingelsson
Ian Deary
Reedik Mägi
Liesbeth Vandenput
Pim van der Harst
Karl Desch
Jaspal Kooner
Claes Ohlsson
Caroline Hayward
Terho Lehtimäki
Alan Shuldiner
Donna Arnett
Lawrence Beilin
Antonietta Robino
Philippe Froguel
Mario Pirastu
Tine Jess
Wolfgang Koenig
Ruth Loos
Denis Evans
Helena Schmidt
George Smith
P Eline Slagboom
Gudny Eiriksdottir
Andrew Morris
Bruce Psaty
Russell Tracy
Ilja Nolte
Eric Boerwinkle
Sophie Visvikis-Siest
Alex Reiner
Myron Gross
Joshua Bis
Lude Franke
Oscar Franco
Emelia Benjamin
Daniel Chasman
Josée Dupuis
Harold Snieder
Abbas Dehghan
Behrooz Alizadeh
Keywords
Female
Humans
Male
Adult
Aged
Middle Aged
Adolescent
Child
Genome-Wide Association Study
Young Adult
Biomarkers
Schizophrenia
Genetic Loci
Metabolic Networks and Pathways
Liver
Aged, 80 and over
Body Mass Index
Bipolar Disorder
Inflammation
Mendelian Randomization Analysis
C-Reactive Protein
Abstract

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

Year of Publication
2018
Journal
Am J Hum Genet
Volume
103
Issue
5
Pages
691-706
Date Published
2018 Nov 01
ISSN
1537-6605
DOI
10.1016/j.ajhg.2018.09.009
PubMed ID
30388399
PubMed Central ID
PMC6218410
Links
Grant list
R01 HL120393 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
MC_UU_00011/1 / MRC_ / Medical Research Council / United Kingdom
P30 AG049638 / AG / NIA NIH HHS / United States
MR/K002414/1 / MRC_ / Medical Research Council / United Kingdom
MC_UP_1605/7 / MRC_ / Medical Research Council / United Kingdom
G9815508 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12013/4 / MRC_ / Medical Research Council / United Kingdom
BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
MR/J012165/1 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
U01 HL120393 / HL / NHLBI NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
MC_PC_15018 / MRC_ / Medical Research Council / United Kingdom
MC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom
U01 DK062370 / DK / NIDDK NIH HHS / United States
P30 DK020572 / DK / NIDDK NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
R01 HL141399 / HL / NHLBI NIH HHS / United States
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom

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