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

J. van Dongen, R. Jansen, D.J.A. Smit, J.J. Hottenga, H. Mbarek, G. Willemsen, C. Kluft, B.W.J.H. Penninx, M.A. Ferreira, D.I. Boomsma, E.J.C. de Geus

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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. © 2014 Springer Science+Business Media.
Original languageEnglish
Pages (from-to)368-382
Number of pages15
JournalBehavior genetics
Issue number4
Publication statusPublished - 2014

Cohort Studies

  • Netherlands Twin Register (NTR)

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