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A characterization of cis- and trans-heritability of RNA-Seq-based gene expression.

ABSTRACT: Insights into individual differences in gene expression and its heritability (h²) can help in understanding pathways from DNA to phenotype. We estimated the heritability of gene expression of 52,844 genes measured in whole blood in the largest twin RNA-Seq sample to date (1497 individuals including 459 monozygotic twin pairs and 150 dizygotic twin pairs) from classical twin modeling and identity-by-state-based approaches. We estimated for each gene h²_total, composed of cis-heritability (h²_cis, the variance explained by single nucleotide polymorphisms in the cis-window of the gene), and trans-heritability (h²_res, the residual variance explained by all other genome-wide variants). Mean h²_total was 0.26, which was significantly higher than heritability estimates earlier found in a microarray-based study using largely overlapping (>60%) RNA samples (mean h²?=?0.14, p?=?6.15?×?10^-258). Mean h²_cis was 0.06 and strongly correlated with beta of the top cis expression quantitative loci (eQTL, ??=?0.76, p?-308) and with estimates from earlier RNA-Seq-based studies. Mean h²_res was 0.20 and correlated with the beta of the corresponding trans-eQTL (??=?0.04, p?-3) and was significantly higher for genes involved in cytokine-cytokine interactions (p?=?4.22?×?10^-15), many other immune system pathways, and genes identified in genome-wide association studies for various traits including behavioral disorders and cancer. This study provides a thorough characterization of cis- and trans-h² estimates of gene expression, which is of value for interpretation of GWAS and gene expression studies.

SUBMITTER: Ouwens KG

PROVIDER: S-EPMC6974598 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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A characterization of cis- and trans-heritability of RNA-Seq-based gene expression.

Ouwens Klaasjan G KG Jansen Rick R Nivard Michel G MG van Dongen Jenny J Frieser Maia J MJ Hottenga Jouke-Jan JJ Arindrarto Wibowo W Claringbould Annique A van Iterson Maarten M Mei Hailiang H Franke Lude L Heijmans Bastiaan T BT A C 't Hoen Peter P van Meurs Joyce J Brooks Andrew I AI Penninx Brenda W J H BWJH Boomsma Dorret I DI

European journal of human genetics : EJHG 20190926 2

Insights into individual differences in gene expression and its heritability (h2) can help in understanding pathways from DNA to phenotype. We estimated the heritability of gene expression of 52,844 genes measured in whole blood in the largest twin RNA-Seq sample to date (1497 individuals including 459 monozygotic twin pairs and 150 dizygotic twin pairs) from classical twin modeling and identity-by-state-based approaches. We estimated for each gene h2total, compo ...[more]

PMID: 31558840

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Project description:BACKGROUND: Common bean (Phaseolus vulgaris) is grown throughout the world and comprises roughly 50% of the grain legumes consumed worldwide. Despite this, genetic resources for common beans have been lacking. Next generation sequencing, has facilitated our investigation of the gene expression profiles associated with biologically important traits in common bean. An increased understanding of gene expression in common bean will improve our understanding of gene expression patterns in other legume species. RESULTS: Combining recently developed genomic resources for Phaseolus vulgaris, including predicted gene calls, with RNA-Seq technology, we measured the gene expression patterns from 24 samples collected from seven tissues at developmentally important stages and from three nitrogen treatments. Gene expression patterns throughout the plant were analyzed to better understand changes due to nodulation, seed development, and nitrogen utilization. We have identified 11,010 genes differentially expressed with a fold change???2 and a P-value?<?0.05 between different tissues at the same time point, 15,752 genes differentially expressed within a tissue due to changes in development, and 2,315 genes expressed only in a single tissue. These analyses identified 2,970 genes with expression patterns that appear to be directly dependent on the source of available nitrogen. Finally, we have assembled this data in a publicly available database, The Phaseolus vulgaris Gene Expression Atlas (Pv GEA), http://plantgrn.noble.org/PvGEA/ . Using the website, researchers can query gene expression profiles of their gene of interest, search for genes expressed in different tissues, or download the dataset in a tabular form. CONCLUSIONS: These data provide the basis for a gene expression atlas, which will facilitate functional genomic studies in common bean. Analysis of this dataset has identified genes important in regulating seed composition and has increased our understanding of nodulation and impact of the nitrogen source on assimilation and distribution throughout the plant.

Dataset Information

A characterization of cis- and trans-heritability of RNA-Seq-based gene expression.

Publications

A characterization of cis- and trans-heritability of RNA-Seq-based gene expression.

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