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

Ligthart, S.; Vaez, A.; Vosa, 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.; Mace, 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.; Lyytikainen, L. P.; Oldmeadow, C.; Deelen, J.; 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.

doi:10.1016/j.ajhg.2018.09.009

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

Ligthart, S., Vaez, A., Vosa, U., Stathopoulou, M. G., de Vries, P. S., Prins, B. P., et al. (2018). 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, 103(5), 691-706. doi:10.1016/j.ajhg.2018.09.009.

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Datensatz-Permalink: https://hdl.handle.net/21.11116/0000-000B-47C1-B Versions-Permalink: https://hdl.handle.net/21.11116/0000-000C-0851-0

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https://www.ncbi.nlm.nih.gov/pubmed/30388399 (beliebiger Volltext) Open Access Status unbekannt

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Ligthart, S., Autor
Vaez, A., Autor
Vosa, U., Autor
Stathopoulou, M. G., Autor
de Vries, P. S., Autor
Prins, B. P., Autor
Van der Most, P. J., Autor
Tanaka, T., Autor
Naderi, E., Autor
Rose, L. M., Autor
Wu, Y., Autor
Karlsson, R., Autor
Barbalic, M., Autor
Lin, H., Autor
Pool, R., Autor
Zhu, G., Autor
Mace, A., Autor
Sidore, C., Autor
Trompet, S., Autor
Mangino, M., Autor
Sabater-Lleal, M., AutorKemp, J. P., AutorAbbasi, A., AutorKacprowski, T., AutorVerweij, N., AutorSmith, A. V., AutorHuang, T., AutorMarzi, C., AutorFeitosa, M. F., AutorLohman, K. K., AutorKleber, M. E., AutorMilaneschi, Y., AutorMueller, C., AutorHuq, M., AutorVlachopoulou, E., AutorLyytikainen, L. P., AutorOldmeadow, C., AutorDeelen, J.¹, Autor Slagboom, P. E., Autor Eiriksdottir, G., AutorMorris, A. P., AutorPsaty, B. M., AutorTracy, R. P., AutorNolte, I. M., AutorBoerwinkle, E., AutorVisvikis-Siest, S., AutorReiner, A. P., AutorGross, M., AutorBis, J. C., AutorFranke, L., AutorFranco, O. H., AutorBenjamin, E. J., AutorChasman, D. I., AutorDupuis, J., AutorSnieder, H., AutorDehghan, A., AutorAlizadeh, B. Z., Autor mehr..

Affiliations:
1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006

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Schlagwörter: Adolescent Adult Aged Aged, 80 and over Biomarkers/metabolism Bipolar Disorder/genetics/metabolism Body Mass Index C-Reactive Protein/genetics Child Female Genetic Loci/*genetics Genome-Wide Association Study/methods Humans Inflammation/*genetics/metabolism Liver/metabolism/pathology Male Mendelian Randomization Analysis/methods Metabolic Networks and Pathways/*genetics Middle Aged Schizophrenia/genetics/metabolism Young Adult *C-reactive protein *depict *Mendelian randomization *coronary artery disease *genome-wide association study *inflammation *inflammatory disorders *schizophrenia *system biology

Zusammenfassung: 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 x 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.

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Datum: Online veröffentlicht: 2018-11-01Erschienen: 2018-11-06

Publikationsstatus: Erschienen

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Identifikatoren: Anderer: 30388399
DOI: 10.1016/j.ajhg.2018.09.009
ISSN: 1537-6605 (Electronic)0002-9297 (Linking)

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Titel: Am J Hum Genet

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Seiten: - Band / Heft: 103 (5) Artikelnummer: - Start- / Endseite: 691 - 706 Identifikator: -

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