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

BIOS Consortium

Research output: Contribution to JournalArticleAcademicpeer-review

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 h2total, composed of cis-heritability (h2cis, the variance explained by single nucleotide polymorphisms in the cis-window of the gene), and trans-heritability (h2res, the residual variance explained by all other genome-wide variants). Mean h2total 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 h2cis was 0.06 and strongly correlated with beta of the top cis expression quantitative loci (eQTL, ρ = 0.76, p < 10-308) and with estimates from earlier RNA-Seq-based studies. Mean h2res was 0.20 and correlated with the beta of the corresponding trans-eQTL (ρ = 0.04, p < 1.89 × 10-3) 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.

Original languageEnglish
JournalEuropean Journal of Human Genetics
DOIs
Publication statusE-pub ahead of print - 26 Sep 2019

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RNA
Gene Expression
Genes
Genome-Wide Association Study
Cytokines
Dizygotic Twins
Monozygotic Twins
Individuality
Single Nucleotide Polymorphism
Immune System
Genome
Phenotype
DNA
Neoplasms

Cite this

@article{af5778c7d66c4847a31cf54a7efd09d4,
title = "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 h2total, composed of cis-heritability (h2cis, the variance explained by single nucleotide polymorphisms in the cis-window of the gene), and trans-heritability (h2res, the residual variance explained by all other genome-wide variants). Mean h2total 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 h2cis was 0.06 and strongly correlated with beta of the top cis expression quantitative loci (eQTL, ρ = 0.76, p < 10-308) and with estimates from earlier RNA-Seq-based studies. Mean h2res was 0.20 and correlated with the beta of the corresponding trans-eQTL (ρ = 0.04, p < 1.89 × 10-3) 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.",
author = "Ouwens, {Klaasjan G} and Rick Jansen and Nivard, {Michel G} and {van Dongen}, Jenny and Frieser, {Maia J} and Jouke-Jan Hottenga and Wibowo Arindrarto and Annique Claringbould and {van Iterson}, Maarten and Hailiang Mei and Lude Franke and Heijmans, {Bastiaan T} and {A C 't Hoen}, Peter and {van Meurs}, Joyce and Brooks, {Andrew I} and Penninx, {Brenda W J H} and Boomsma, {Dorret I} and {BIOS Consortium}",
year = "2019",
month = "9",
day = "26",
doi = "10.1038/s41431-019-0511-5",
language = "English",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "Nature Publishing Group",

}

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

In: European Journal of Human Genetics, 26.09.2019.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - A characterization of cis- and trans-heritability of RNA-Seq-based gene expression

AU - Ouwens, Klaasjan G

AU - Jansen, Rick

AU - Nivard, Michel G

AU - van Dongen, Jenny

AU - Frieser, Maia J

AU - Hottenga, Jouke-Jan

AU - Arindrarto, Wibowo

AU - Claringbould, Annique

AU - van Iterson, Maarten

AU - Mei, Hailiang

AU - Franke, Lude

AU - Heijmans, Bastiaan T

AU - A C 't Hoen, Peter

AU - van Meurs, Joyce

AU - Brooks, Andrew I

AU - Penninx, Brenda W J H

AU - Boomsma, Dorret I

AU - BIOS Consortium

PY - 2019/9/26

Y1 - 2019/9/26

N2 - 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, composed of cis-heritability (h2cis, the variance explained by single nucleotide polymorphisms in the cis-window of the gene), and trans-heritability (h2res, the residual variance explained by all other genome-wide variants). Mean h2total 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 h2cis was 0.06 and strongly correlated with beta of the top cis expression quantitative loci (eQTL, ρ = 0.76, p < 10-308) and with estimates from earlier RNA-Seq-based studies. Mean h2res was 0.20 and correlated with the beta of the corresponding trans-eQTL (ρ = 0.04, p < 1.89 × 10-3) 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.

AB - 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, composed of cis-heritability (h2cis, the variance explained by single nucleotide polymorphisms in the cis-window of the gene), and trans-heritability (h2res, the residual variance explained by all other genome-wide variants). Mean h2total 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 h2cis was 0.06 and strongly correlated with beta of the top cis expression quantitative loci (eQTL, ρ = 0.76, p < 10-308) and with estimates from earlier RNA-Seq-based studies. Mean h2res was 0.20 and correlated with the beta of the corresponding trans-eQTL (ρ = 0.04, p < 1.89 × 10-3) 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.

U2 - 10.1038/s41431-019-0511-5

DO - 10.1038/s41431-019-0511-5

M3 - Article

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

ER -