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

Details

Serval ID
serval:BIB_26357D5FDD21
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.
Journal
American journal of human genetics
Author(s)
Ligthart S., Vaez A., Võsa U., Stathopoulou M.G., de Vries P.S., Prins B.P., Van der Most P.J., Tanaka T., Naderi E., Rose L.M., Wu Y., Karlsson R., Barbalic M., Lin H., Pool R., Zhu G., Macé A., Sidore C., Trompet S., Mangino M., Sabater-Lleal M., Kemp J.P., Abbasi A., Kacprowski T., Verweij N., Smith A.V., Huang T., Marzi C., Feitosa M.F., Lohman K.K., Kleber M.E., Milaneschi Y., Mueller C., Huq M., Vlachopoulou E., Lyytikäinen L.P., Oldmeadow C., Deelen J., Perola M., Zhao J.H., Feenstra B., Amini M., Lahti J., Schraut K.E., Fornage M., Suktitipat B., Chen W.M., Li X., Nutile T., Malerba G., Luan J., Bak T., Schork N., Del Greco M F., Thiering E., Mahajan A., Marioni R.E., Mihailov E., Eriksson J., Ozel A.B., Zhang W., Nethander M., Cheng Y.C., Aslibekyan S., Ang W., Gandin I., Yengo L., Portas L., Kooperberg C., Hofer E., Rajan K.B., Schurmann C., den Hollander W., Ahluwalia T.S., Zhao J., Draisma HHM, Ford I., Timpson N., Teumer A., Huang H., Wahl S., Liu Y., Huang J., Uh H.W., Geller F., Joshi P.K., Yanek L.R., Trabetti E., Lehne B., Vozzi D., Verbanck M., Biino G., Saba Y., Meulenbelt I., O'Connell J.R., Laakso M., Giulianini F., Magnusson PKE, Ballantyne C.M., Hottenga J.J., Montgomery G.W., Rivadineira F., Rueedi R., Steri M., Herzig K.H., Stott D.J., Menni C., Frånberg M., St Pourcain B., Felix S.B., Pers T.H., Bakker SJL, Kraft P., Peters A., Vaidya D., Delgado G., Smit J.H., Großmann V., Sinisalo J., Seppälä I., Williams S.R., Holliday E.G., Moed M., Langenberg C., Räikkönen K., Ding J., Campbell H., Sale M.M., Chen Y.I., James A.L., Ruggiero D., Soranzo N., Hartman C.A., Smith E.N., Berenson G.S., Fuchsberger C., Hernandez D., Tiesler CMT, Giedraitis V., Liewald D., Fischer K., Mellström D., Larsson A., Wang Y., Scott W.R., Lorentzon M., Beilby J., Ryan K.A., Pennell C.E., Vuckovic D., Balkau B., Concas M.P., Schmidt R., Mendes de Leon C.F., Bottinger E.P., Kloppenburg M., Paternoster L., Boehnke M., Musk A.W., Willemsen G., Evans D.M., Madden PAF, Kähönen M., Kutalik Z., Zoledziewska M., Karhunen V., Kritchevsky S.B., Sattar N., Lachance G., Clarke R., Harris T.B., Raitakari O.T., Attia J.R., van Heemst D., Kajantie E., Sorice R., Gambaro G., Scott R.A., Hicks A.A., Ferrucci L., Standl M., Lindgren C.M., Starr J.M., Karlsson M., Lind L., Li J.Z., Chambers J.C., Mori T.A., de Geus EJCN, Heath A.C., Martin N.G., Auvinen J., Buckley B.M., de Craen AJM, Waldenberger M., Strauch K., Meitinger T., Scott R.J., McEvoy M., Beekman M., Bombieri C., Ridker P.M., Mohlke K.L., Pedersen N.L., Morrison A.C., Boomsma D.I., Whitfield J.B., Strachan D.P., Hofman A., Vollenweider P., Cucca F., Jarvelin M.R., Jukema J.W., Spector T.D., Hamsten A., Zeller T., Uitterlinden A.G., Nauck M., Gudnason V., Qi L., Grallert H., Borecki I.B., Rotter J.I., März W., Wild P.S., Lokki M.L., Boyle M., Salomaa V., Melbye M., Eriksson J.G., Wilson J.F., Penninx BWJH, Becker D.M., Worrall B.B., Gibson G., Krauss R.M., Ciullo M., Zaza G., Wareham N.J., Oldehinkel A.J., Palmer L.J., Murray S.S., Pramstaller P.P., Bandinelli S., Heinrich J., Ingelsson E., Deary I.J., Mägi R., Vandenput L., van der Harst P., Desch K.C., Kooner J.S., Ohlsson C., Hayward C., Lehtimäki T., Shuldiner A.R., Arnett D.K., Beilin L.J., Robino A., Froguel P., Pirastu M., Jess T., Koenig W., Loos RJF, Evans D.A., Schmidt H., Smith G.D., Slagboom P.E., Eiriksdottir G., Morris A.P., Psaty B.M., Tracy R.P., Nolte I.M., Boerwinkle E., Visvikis-Siest S., Reiner A.P., Gross M., Bis J.C., Franke L., Franco O.H., Benjamin E.J., Chasman D.I., Dupuis J., Snieder H., Dehghan A., Alizadeh B.Z.
Working group(s)
LifeLines Cohort Study, CHARGE Inflammation Working Group
Contributor(s)
Alizadeh B.Z., Boezen H.M., Franke L., van der Harst P., Navis G., Rots M., Snieder H., Swertz M., Wolffenbuttel BHR, Wijmenga C., Benjamin E., Chasman D.I., Dehghan A., Ahluwalia T.S., Meigs J., Tracy R., Alizadeh B.Z., Ligthart S., Bis J., Eiriksdottir G., Pankratz N., Gross M., Rainer A., Snieder H., Wilson J.G., Psaty B.M., Dupuis J., Prins B., Vaso U., Stathopoulou M., Franke L., Lehtimaki T., Koenig W., Jamshidi Y., Siest S., Abbasi A., Uitterlinden A.G., Abdollahi M., Schnabel R., Schick U.M., Nolte I.M., Kraja A., Hsu Y.H., Tylee D.S., Zwicker A., Uher R., Davey-Smith G., Morrison A.C., Hicks A., van Duijn C.M., Ward-Caviness C., Boerwinkle E., Rotter J., Rice K., Lange L., Perola M., de Geus E., Morris A.P., Makela K.M., Stacey D., Eriksson J., Frayling T.M., Slagboom E.P.
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Publication state
Published
Issued date
01/11/2018
Peer-reviewed
Oui
Volume
103
Number
5
Pages
691-706
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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 < 5 × 10 <sup>-8</sup> ). 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.
Keywords
Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers/metabolism, Bipolar Disorder/genetics, Bipolar Disorder/metabolism, Body Mass Index, C-Reactive Protein/genetics, Child, Female, Genetic Loci/genetics, Genome-Wide Association Study/methods, Humans, Inflammation/genetics, Inflammation/metabolism, Liver/metabolism, Liver/pathology, Male, Mendelian Randomization Analysis/methods, Metabolic Networks and Pathways/genetics, Middle Aged, Schizophrenia/genetics, Schizophrenia/metabolism, Young Adult, C-reactive protein, DEPICT, Mendelian randomization, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, schizophrenia, system biology
Pubmed
Web of science
Open Access
Yes
Create date
15/11/2018 11:16
Last modification date
20/08/2019 13:04
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