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Strong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs

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  • Stefan Enroth

    (Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University, SE-75108 Uppsala, Sweden)

  • Åsa Johansson

    (Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University, SE-75108 Uppsala, Sweden
    Uppsala Clinical Research Centre, Uppsala University)

  • Sofia Bosdotter Enroth

    (Uppsala University)

  • Ulf Gyllensten

    (Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University, SE-75108 Uppsala, Sweden)

Abstract

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.

Suggested Citation

  • Stefan Enroth & Åsa Johansson & Sofia Bosdotter Enroth & Ulf Gyllensten, 2014. "Strong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5684
    DOI: 10.1038/ncomms5684
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    Cited by:

    1. Karsten Suhre & Guhan Ram Venkataraman & Harendra Guturu & Anna Halama & Nisha Stephan & Gaurav Thareja & Hina Sarwath & Khatereh Motamedchaboki & Margaret K. R. Donovan & Asim Siddiqui & Serafim Batz, 2024. "Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Marcin Kierczak & Nima Rafati & Julia Höglund & Hadrien Gourlé & Valeria Lo Faro & Daniel Schmitz & Weronica E. Ek & Ulf Gyllensten & Stefan Enroth & Diana Ekman & Björn Nystedt & Torgny Karlsson & Ås, 2022. "Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Anders Mälarstig & Felix Grassmann & Leo Dahl & Marios Dimitriou & Dianna McLeod & Marike Gabrielson & Karl Smith-Byrne & Cecilia E. Thomas & Tzu-Hsuan Huang & Simon K. G. Forsberg & Per Eriksson & Mi, 2023. "Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    4. Jonathan D. Mosley & John P. Shelley & Alyson L. Dickson & Jacy Zanussi & Laura L. Daniel & Neil S. Zheng & Lisa Bastarache & Wei-Qi Wei & Mingjian Shi & Gail P. Jarvik & Elisabeth A. Rosenthal & Atla, 2024. "Clinical associations with a polygenic predisposition to benign lower white blood cell counts," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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