Behavior Genetics

, Volume 44, Issue 4, pp 368–382

The Contribution of the Functional IL6R Polymorphism rs2228145, eQTLs and Other Genome-Wide SNPs to the Heritability of Plasma sIL-6R Levels

Authors

    • Department of Biological PsychologyVU University Amsterdam
    • EMGO Institute for Health and Care ResearchVU University Medical Center
  • Rick Jansen
    • Department of PsychiatryVU University Medical Center
    • Neuroscience Campus Amsterdam
  • Dirk Smit
    • Department of Biological PsychologyVU University Amsterdam
    • Neuroscience Campus Amsterdam
  • Jouke-Jan Hottenga
    • Department of Biological PsychologyVU University Amsterdam
    • EMGO Institute for Health and Care ResearchVU University Medical Center
  • Hamdi Mbarek
    • Department of Biological PsychologyVU University Amsterdam
    • EMGO Institute for Health and Care ResearchVU University Medical Center
  • Gonneke Willemsen
    • Department of Biological PsychologyVU University Amsterdam
    • EMGO Institute for Health and Care ResearchVU University Medical Center
  • Cornelis Kluft
    • Good Biomarker Sciences
  • AAGC Collaborators
  • Brenda W. J. Penninx
    • EMGO Institute for Health and Care ResearchVU University Medical Center
    • Department of PsychiatryVU University Medical Center
    • Neuroscience Campus Amsterdam
  • Manuel A. Ferreira
    • Queensland Institute of Medical Research
  • Dorret I. Boomsma
    • Department of Biological PsychologyVU University Amsterdam
    • EMGO Institute for Health and Care ResearchVU University Medical Center
    • Neuroscience Campus Amsterdam
  • Eco J. C. de Geus
    • Department of Biological PsychologyVU University Amsterdam
    • EMGO Institute for Health and Care ResearchVU University Medical Center
Original Research

DOI: 10.1007/s10519-014-9656-8

Cite this article as:
van Dongen, J., Jansen, R., Smit, D. et al. Behav Genet (2014) 44: 368. doi:10.1007/s10519-014-9656-8

Abstract

The non-synonymous SNP rs2228145 in the IL6R gene on chromosome 1q21.3 is associated with a wide range of common diseases, including asthma, rheumatoid arthritis, type 1 diabetes and coronary heart disease. We examined the contribution of this functional IL6R gene polymorphism rs2228145 versus other genome-wide SNPs to the variance of sIL-6R levels in blood plasma in a large population-based sample (N ~5,000), and conducted an expression QTL analysis to identify SNPs associated with IL6R gene expression. Based on data from 2,360 twin families, the broad heritability of sIL-6R was estimated at 72 and 51 % of the total variance was explained by the functional SNP rs2228145. Converging findings from GWAS, linkage, and GCTA analyses indicate that additional variance of sIL-6R levels can be explained by other variants in the IL6R region, including variants at the 3′-end of IL6R tagged by rs60760897 that are associated with IL6R RNA expression.

Keywords

Soluble interleukin-6 receptorInflammationHeritabilityGWASGene expressioneQTL

Supplementary material

10519_2014_9656_MOESM1_ESM.pdf (4.8 mb)
Supplementary material 1 (PDF 4919 kb)

Copyright information

© Springer Science+Business Media New York 2014