title: The contribution of the functional IL6R polymorphism rs2228145, eQTLs and other genome-wide SNPs to the heritability of plasma sIL-6R levels.
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.
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands, j.van.dongen@vu.nl.
authors.forename: Jenny
authors.initials: J
authors.lastname: van Dongen
authors.forename: Rick
authors.initials: R
authors.lastname: Jansen
authors.forename: Dirk
authors.initials: D
authors.lastname: Smit
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.forename: Hamdi
authors.initials: H
authors.lastname: Mbarek
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.forename: Cornelis
authors.initials: C
authors.lastname: Kluft
authors.forename: Brenda W J
authors.initials: BW
authors.lastname: Penninx
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Ferreira
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D009426:Netherlands; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D019947:Receptors, Interleukin-6 / Q000097:blood* / Q000235:genetics*
chemical_list: D019947:Receptors, Interleukin-6