The contribution of the functional IL6R polymorphism rs2228145, eQTLs and other genome-wide SNPs to the heritability of plasma sIL-6R levels

Behav Genet. 2014 Jul;44(4):368-82. doi: 10.1007/s10519-014-9656-8. Epub 2014 May 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Netherlands
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci / genetics*
  • Receptors, Interleukin-6 / blood*
  • Receptors, Interleukin-6 / genetics*


  • Receptors, Interleukin-6