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

• Published in: Behavior genetics Vol. 44; no. 4; pp. 368 - 382
• Main Authors: van Dongen, Jenny, Jansen, Rick, Smit, Dirk, Hottenga, Jouke-Jan, Mbarek, Hamdi, Willemsen, Gonneke, Kluft, Cornelis, Penninx, Brenda W. J., Ferreira, Manuel A., Boomsma, Dorret I., de Geus, Eco J. C.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.07.2014; Springer Nature B.V
• Subjects: Asthma; Behavioral Science and Psychology; Cardiovascular disease; Clinical Psychology; Collaboration; Consortia; Cytokines; Diabetes; Enzyme-Linked Immunosorbent Assay; Female; Gene expression; Genetics; Genome-Wide Association Study; Genomes; Genotype; Health Psychology; Humans; Ligands; Male; Netherlands; Oligonucleotide Array Sequence Analysis; Original Research; Plasma; Polymorphism; Polymorphism, Single Nucleotide; Psychology; Public Health; Quantitative Trait Loci - genetics; Receptors, Interleukin-6 - blood; Receptors, Interleukin-6 - genetics; Rheumatoid arthritis; Risk factors; Signal transduction; Netherlands; Soluble interleukin-6 receptor; Inflammation; Heritability; GWAS; eQTL; Gene expression
• ISSN: 0001-8244; 1573-3297
• DOI: 10.1007/s10519-014-9656-8

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.