title: Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.
abstract: BACKGROUND
  C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels.
  
  
  RESULTS
  We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2) or the immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1) or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found a significant interaction of body mass index with LEPR (P<2.9×10(-6)). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained ≈5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease.
  
  
  CONCLUSIONS
  We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.
authors.affiliation: Erasmus Medical Center, Dr Molewaterplein 50, Rotterdam, Netherlands.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.forename: Maja
authors.initials: M
authors.lastname: Barbalic
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: Gudny
authors.initials: G
authors.lastname: Eiriksdottir
authors.forename: Chen
authors.initials: C
authors.lastname: Lu
authors.forename: Niina
authors.initials: N
authors.lastname: Pellikka
authors.forename: Henri
authors.initials: H
authors.lastname: Wallaschofski
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.forename: Peter
authors.initials: P
authors.lastname: Henneman
authors.forename: Jens
authors.initials: J
authors.lastname: Baumert
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Christian
authors.initials: C
authors.lastname: Fuchsberger
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.forename: Guillaume
authors.initials: G
authors.lastname: Paré
authors.forename: Silvia
authors.initials: S
authors.lastname: Naitza
authors.forename: Megan E
authors.initials: ME
authors.lastname: Rudock
authors.forename: Ida
authors.initials: I
authors.lastname: Surakka
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.forename: Behrooz Z
authors.initials: BZ
authors.lastname: Alizadeh
authors.forename: Jack
authors.initials: J
authors.lastname: Guralnik
authors.forename: Alan
authors.initials: A
authors.lastname: Shuldiner
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Robert Y L
authors.initials: RY
authors.lastname: Zee
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.forename: Vijay
authors.initials: V
authors.lastname: Nambi
authors.forename: Maryam
authors.initials: M
authors.lastname: Kavousi
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.forename: Albert V
authors.initials: AV
authors.lastname: Smith
authors.forename: Jouko
authors.initials: J
authors.lastname: Sundvall
authors.forename: Paul
authors.initials: P
authors.lastname: Scheet
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Rose
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Freimer
authors.forename: Alexander
authors.initials: A
authors.lastname: Teumer
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Yamamoto
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.forename: James
authors.initials: J
authors.lastname: Pankow
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
authors.forename: John F
authors.initials: JF
authors.lastname: Keaney
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Antti-Pekka
authors.initials: AP
authors.lastname: Sarin
authors.forename: João D
authors.initials: JD
authors.lastname: Fontes
authors.forename: Sunita
authors.initials: S
authors.lastname: Badola
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Anneli
authors.initials: A
authors.lastname: Pouta
authors.forename: Karl
authors.initials: K
authors.lastname: Werdan
authors.forename: Karin H
authors.initials: KH
authors.lastname: Greiser
authors.forename: Oliver
authors.initials: O
authors.lastname: Kuss
authors.forename: Henriette E
authors.initials: HE
authors.lastname: Meyer zu Schwabedissen
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Yalda
authors.initials: Y
authors.lastname: Jamshidi
authors.forename: Ilja M
authors.initials: IM
authors.lastname: Nolte
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Parker
authors.forename: Thor
authors.initials: T
authors.lastname: Aspelund
authors.forename: David
authors.initials: D
authors.lastname: Bates
authors.forename: Lauren
authors.initials: L
authors.lastname: Young
authors.forename: Kim
authors.initials: K
authors.lastname: Tsui
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Manuela
authors.initials: M
authors.lastname: Uda
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Hicks
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Penninx
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Joe
authors.initials: J
authors.lastname: Coresh
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rice
authors.forename: Dörte
authors.initials: D
authors.lastname: Radke
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Ko
authors.initials: K
authors.lastname: Willems van Dijk
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Quince D
authors.initials: QD
authors.lastname: Gibson
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Xiao
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
mesh_terms: D015415:Biomarkers; D002097:C-Reactive Protein / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D006801:Humans; D012307:Risk Factors; D014657:Vasculitis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein