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@article{Ligthart:2018:10.1016/j.ajhg.2018.09.009,
author = {Ligthart, S and Vaez, A and Vosa, U and Stathopoulou, MG and de, Vries PS and Prins, BP and Van, der Most PJ and Tanaka, T and Naderi, E and Rose, LM and Wu, Y and Karlsson, R and Barbalic, M and Lin, H and Pool, R and Zhu, G and Mace, A and Sidore, C and Trompet, S and Mangino, M and Sabater-Lleal, M and Kemp, JP and Abbasi, A and Kacprowski, T and Verweij, N and Smith, AV and Huang, T and Marzi, C and Feitosa, MF and Lohman, KK and Kleber, ME and Milaneschi, Y and Mueller, C and Huq, M and Vlachopoulou, E and Lyytikainen, L-P and Oldmeadow, C and Deelen, J and Perola, M and Zhao, JH and Feenstra, B and Amini, M and Lahti, J and Schraut, KE and Fornage, M and Suktitipat, B and Chen, W-M and Li, X and Nutile, T and Malerba, G and Luan, J and Bak, T and Schork, N and Del, Greco FM and Thiering, E and Mahajan, A and Marioni, RE and Mihailov, E and Eriksson, J and Ozel, AB and Zhang, W and Nethander, M and Cheng, Y-C and Aslibekyan, S and Ang, W and Gandin, I and Yengo, L and Portas, L an},
doi = {10.1016/j.ajhg.2018.09.009},
journal = {American Journal of Human Genetics},
pages = {691--706},
title = {Genome analyses of >200,000 individuals identify 58 loci for chronic inflammation and highlight pathways that link inflammation and complex disorders},
url = {http://dx.doi.org/10.1016/j.ajhg.2018.09.009},
volume = {103},
year = {2018}
}

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TY  - JOUR
AB  - 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.
AU  - Ligthart,S
AU  - Vaez,A
AU  - Vosa,U
AU  - Stathopoulou,MG
AU  - de,Vries PS
AU  - Prins,BP
AU  - Van,der Most PJ
AU  - Tanaka,T
AU  - Naderi,E
AU  - Rose,LM
AU  - Wu,Y
AU  - Karlsson,R
AU  - Barbalic,M
AU  - Lin,H
AU  - Pool,R
AU  - Zhu,G
AU  - Mace,A
AU  - Sidore,C
AU  - Trompet,S
AU  - Mangino,M
AU  - Sabater-Lleal,M
AU  - Kemp,JP
AU  - Abbasi,A
AU  - Kacprowski,T
AU  - Verweij,N
AU  - Smith,AV
AU  - Huang,T
AU  - Marzi,C
AU  - Feitosa,MF
AU  - Lohman,KK
AU  - Kleber,ME
AU  - Milaneschi,Y
AU  - Mueller,C
AU  - Huq,M
AU  - Vlachopoulou,E
AU  - Lyytikainen,L-P
AU  - Oldmeadow,C
AU  - Deelen,J
AU  - Perola,M
AU  - Zhao,JH
AU  - Feenstra,B
AU  - Amini,M
AU  - Lahti,J
AU  - Schraut,KE
AU  - Fornage,M
AU  - Suktitipat,B
AU  - Chen,W-M
AU  - Li,X
AU  - Nutile,T
AU  - Malerba,G
AU  - Luan,J
AU  - Bak,T
AU  - Schork,N
AU  - Del,Greco FM
AU  - Thiering,E
AU  - Mahajan,A
AU  - Marioni,RE
AU  - Mihailov,E
AU  - Eriksson,J
AU  - Ozel,AB
AU  - Zhang,W
AU  - Nethander,M
AU  - Cheng,Y-C
AU  - Aslibekyan,S
AU  - Ang,W
AU  - Gandin,I
AU  - Yengo,L
AU  - Portas,L
AU  - Kooperberg,C
AU  - Hofer,E
AU  - Rajan,KB
AU  - Schurmann,C
AU  - den,Hollander W
AU  - Ahluwalia,TS
AU  - Zhao,J
AU  - Draisma,HHM
AU  - Ford,I
AU  - Timpson,N
AU  - Teumer,A
AU  - Huang,H
AU  - Wahl,S
AU  - Liu,Y
AU  - Huang,J
AU  - Uh,H-W
AU  - Geller,F
AU  - Joshi,PK
AU  - Yanek,LR
AU  - Trabetti,E
AU  - Lehne,B
AU  - Vozzi,D
AU  - Verbanck,M
AU  - Biino,G
AU  - Saba,Y
AU  - Meulenbelt,I
AU  - O'Connell,JR
AU  - Laakso,M
AU  - Giulianini,F
AU  - Magnusson,PKE
AU  - Ballantyne,CM
AU  - Hottenga,JJ
AU  - Montgomery,G
AU  - Rivadineira,F
AU  - Rueedi,R
AU  - Steri,M
AU  - Herzig,K-H
AU  - Stott,DJ
AU  - Menni,C
AU  - Franberg,M
AU  - St,Pourcain B
AU  - Felix,SB
AU  - Pers,TH
AU  - Bakker,SJL
AU  - Kraft,P
AU  - Peters,A
AU  - Vaidya,D
AU  - Delgado,G
AU  - Smit,JH
AU  - Grossmann,V
AU  - Sinisalo,J
AU  - Seppala,I
AU  - Williams,SR
AU  - Holliday,EG
AU  - Moed,M
AU  - Langenberg,C
AU  - Raikkonen,K
AU  - Ding,J
AU  - Campbell,H
AU  - Sale,MM
AU  - Chen,Y-DI
AU  - James,AL
AU  - Ruggiero,D
AU  - Soranzo,N
AU  - Hartman,CA
AU  - Smith,EN
AU  - Berenson,GS
AU  - Fuchsberger,C
AU  - Hernandez,D
AU  - Tiesler,CMT
AU  - Giedraitis,V
AU  - Liewald,D
AU  - Fischer,K
AU  - Mellstrom,D
AU  - Larsson,A
AU  - Wang,Y
AU  - Scott,WR
AU  - Lorentzon,M
AU  - Beilby,J
AU  - Ryan,KA
AU  - Pennell,CE
AU  - Vuckovic,D
AU  - Balkau,B
AU  - Concas,MP
AU  - Schmidt,R
AU  - de,Leon CFM
AU  - Bottinger,EP
AU  - Kloppenburg,M
AU  - Paternoster,L
AU  - Boehnke,M
AU  - Musk,AW
AU  - Willemsen,G
AU  - Evans,DM
AU  - Madden,PAF
AU  - Kahonen,M
AU  - Kutalik,Z
AU  - Zoledziewska,M
AU  - Karhunen,V
AU  - Kritchevsky,SB
AU  - Sattar,N
AU  - Lachance,G
AU  - Clarke,R
AU  - Harris,TB
AU  - Raitakari,OT
AU  - Attia,JR
AU  - Van,Heemst D
AU  - Kajantie,E
AU  - Sorice,R
AU  - Gambaro,G
AU  - Scott,RA
AU  - Hicks,AA
AU  - Ferrucci
DO  - 10.1016/j.ajhg.2018.09.009
EP  - 706
PY  - 2018///
SN  - 0002-9297
SP  - 691
TI  - Genome analyses of >200,000 individuals identify 58 loci for chronic inflammation and highlight pathways that link inflammation and complex disorders
T2  - American Journal of Human Genetics
UR  - http://dx.doi.org/10.1016/j.ajhg.2018.09.009
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000448942100006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/64725
VL  - 103
ER  -

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