Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
Show others and affiliations
2018 (English)In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 103, no 5, p. 691-706, article id S0002-9297(18)30320-3Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2018. Vol. 103, no 5, p. 691-706, article id S0002-9297(18)30320-3
Keywords [en]
C-reactive protein, DEPICT, Mendelian randomization, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, schizophrenia, system biology
National Category
Public Health, Global Health, Social Medicine and Epidemiology Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-364795DOI: 10.1016/j.ajhg.2018.09.009ISI: 000448942100006PubMedID: 30388399OAI: oai:DiVA.org:uu-364795DiVA, id: diva2:1260531
Available from: 2018-11-03 Created: 2018-11-03 Last updated: 2019-01-08Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Giedraitis, VilmantasLarsson, AndersLind, LarsIngelsson, Erik
By organisation
GeriatricsClinical ChemistryClinical EpidemiologyMolecular epidemiologyScience for Life Laboratory, SciLifeLab
In the same journal
American Journal of Human Genetics
Public Health, Global Health, Social Medicine and EpidemiologyMedical Genetics

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 93 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf