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
Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands,
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.
位于1号染色体1q21.3区域的IL6R基因中的非同义单核苷酸多态性（SNP）rs2228145与多种常见疾病相关，包括哮喘、类风湿性关节炎、1型糖尿病和冠心病。我们在一个基于人群的大样本（N约5000）中研究了这种功能性IL6R基因多态性rs2228145与其他全基因组SNP对血浆中可溶性IL-6受体（sIL-6R）水平方差的贡献，并进行了表达定量性状位点（eQTL）分析以鉴定与IL6R基因表达相关的SNP。基于来自2360个双胞胎家庭的数据，sIL-6R的广义遗传率估计为72%，总方差的51%可由功能性SNP rs2228145解释。全基因组关联研究（GWAS）、连锁分析和全基因组复杂性状分析（GCTA）的一致结果表明，sIL-6R水平的额外方差可由IL6R区域中的其他变异解释，包括由rs60760897标记的与IL6R RNA表达相关的IL6R 3'端变异。
