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Strong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab. (Gyllensten)ORCID iD: 0000-0002-5056-9137
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
2014 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 5, 4684- p.Article in journal (Refereed) Published
Abstract [en]

Ideal biomarkers used for disease diagnosis should display deviating levels in affected individuals only and be robust to factors unrelated to the disease. Here we show the impact of genetic, clinical and lifestyle factors on circulating levels of 92 protein biomarkers for cancer and inflammation, using a population-based cohort of 1,005 individuals. For 75% of the biomarkers, the levels are significantly heritable and genome-wide association studies identifies 16 novel loci and replicate 2 previously known loci with strong effects on one or several of the biomarkers with P-values down to 4.4 × 10−58. Integrative analysis attributes as much as 56.3% of the observed variance to non-disease factors. We propose that information on the biomarker-specific profile of major genetic, clinical and lifestyle factors should be used to establish personalized clinical cutoffs, and that this would increase the sensitivity of using biomarkers for prediction of clinical end points.

Place, publisher, year, edition, pages
2014. Vol. 5, 4684- p.
National Category
Genetics
Identifiers
URN: urn:nbn:se:uu:diva-230638DOI: 10.1038/ncomms5684ISI: 000341077900009PubMedID: 25147954OAI: oai:DiVA.org:uu-230638DiVA: diva2:741187
Available from: 2014-08-27 Created: 2014-08-27 Last updated: 2017-12-05Bibliographically approved

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Enroth, StefanJohansson, ÅsaBosdotter Enroth, SofiaGyllensten, Ulf

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