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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.

SUBMITTER: van Dongen J

PROVIDER: S-EPMC4283105 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

van Dongen Jenny J Jansen Rick R Smit Dirk D Hottenga Jouke-Jan JJ Mbarek Hamdi H Willemsen Gonneke G Kluft Cornelis C Penninx Brenda W J BW Ferreira Manuel A MA Boomsma Dorret I DI de Geus Eco J C EJ

Behavior genetics 20140503 4

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 ex ...[more]

PMID: 24791950

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Project description:BackgroundWhile the possible sources underlying the so-called 'missing heritability' evident in current genome-wide association studies (GWAS) of complex traits have been actively pursued in recent years, resolving this mystery remains a challenging task. Studying heritability of genome-wide gene expression traits can shed light on the goal of understanding the relationship between phenotype and genotype. Here we used microarray gene expression measurements of lymphoblastoid cell lines and genome-wide SNP genotype data from 210 HapMap individuals to examine the heritability of gene expression traits.ResultsHeritability levels for expression of 10,720 genes were estimated by applying variance component model analyses and 1,043 expression quantitative loci (eQTLs) were detected. Our results indicate that gene expression traits display a bimodal distribution of heritability, one peak close to 0% and the other summit approaching 100%. Such a pattern of the within-population variability of gene expression heritability is common among different HapMap populations of unrelated individuals but different from that obtained in the CEU and YRI trio samples. Higher heritability levels are shown by housekeeping genes and genes associated with cis eQTLs. Both cis and trans eQTLs make comparable cumulative contributions to the heritability. Finally, we modelled gene-gene interactions (epistasis) for genes with multiple eQTLs and revealed that epistasis was not prevailing in all genes but made a substantial contribution in explaining total heritability for some genes analysed.ConclusionsWe utilised a mixed effect model analysis for estimating genetic components from population based samples. On basis of analyses of genome-wide gene expression from four HapMap populations, we demonstrated detailed exploitation of the distribution of genetic heritabilities for expression traits from different populations, and highlighted the importance of studying interaction at the gene expression level as an important source of variation underlying missing heritability.

Dataset Information

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

Publications

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

Similar Datasets

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